Friday, June 26, 2015

Press Release for Acute Type Porphyria and Research: From Alnylam Phase 1 Clinical Trial Drug

Press Release for Acute Type Porphyria and Research:  From                              Alnylam Phase 1 Clinical Trial Drug

Alnylam Initiates Phase 1 Clinical Trial for ALN-AS1, an Investigational RNAi Therapeutic Targeting Aminolevulinic Acid Synthase 1 (ALAS1) for the Treatment of Acute Hepatic Porphyrias, Including Acute Intermittent Porphyria (AIP)


- Company Expects to Present Initial Clinical Results in Early 2016 -
CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Alnylam Pharmaceuticals, Inc. (Nasdaq:ALNY), a leading RNAi therapeutics company, announced today that it has initiated a Phase 1 clinical trial with ALN-AS1, a subcutaneously administered investigational RNAi therapeutic targeting aminolevulinic acid synthase 1 (ALAS1) for the treatment of acute hepatic porphyrias, including acute intermittent porphyria (AIP). The Phase 1 trial of ALN-AS1 will be conducted initially in AIP patients who are asymptomatic "high excreters" (ASHE). These ASHE subjects have a defined mutation in the porphobilinogen deaminase (PBGD) gene and elevated urinary levels of aminolevulinic acid (ALA) and porphobilinogen (PBG), but do not have a current history of porphyria attacks or disease activity. Subsequently, the trial is designed to enroll AIP patients who experience recurrent porphyria attacks. The company expects to present initial clinical data from this trial in early 2016.
"We believe ALN-AS1 has the potential to be a transformative therapy for patients with acute hepatic porphyrias, a group of ultra-rare monogenic diseases with enormous unmet medical need, and we're excited to now advance this innovative investigational medicine to the clinic. Our Phase 1 study aims to obtain data on safety and tolerability in addition to potential clinical activity in ASHE subjects and AIP patients with recurrent attacks," said Akshay Vaishnaw, M.D., Ph.D., Executive Vice President of R&D and Chief Medical Officer of Alnylam. "We're encouraged by the potential for ALN-AS1 to make a difference in the lives of people afflicted with acute hepatic porphyrias. In pre-clinical studies performed in rodent models of AIP, we have shown that subcutaneous administration of ALN-AS1 results in complete suppression of the toxic heme biosynthesis intermediates that cause disease symptoms and pathology. We very much look forward to the advancement of ALN-AS1 in the clinic and expect to share initial data from the Phase 1 trial in early 2016."
"Patients with AIP often present with acute, and at times recurrent attacks that are characterized by severe abdominal pain, neuropathy, neuropsychiatric manifestations, and, in very severe cases, paralysis and respiratory failure. Novel therapies are needed for porphyria patients who suffer from recurrent attacks. These patients can spend a significant number of days in the hospital every month and have a very poor quality of life," said Eliane Sardh, M.D., Ph.D., Senior Physician at the Porphyria Centre Sweden and the Centre for Inherited Metabolic Diseases and Department of Endocrinology, Metabolism and Diabetes at Karolinska University Hospital in Stockholm, Sweden. "I am encouraged with the pre-clinical data to date with ALN-AS1, which I believe support the potential for an RNAi therapeutic as a novel therapeutic option for patients with AIP and other acute hepatic porphyrias."
ALN-AS1 is a subcutaneously administered, investigational RNAi therapeutic that employs Alnylam's ESC-GalNAc delivery technology. ESC-GalNAc-siRNA conjugates are designed to achieve targeted delivery of RNAi therapeutic to hepatocytes through uptake by the asialoglycoprotein receptor, and enable subcutaneous dosing with increased potency and durability and a wide therapeutic index. In pre-clinical studies, multi-dose administration of ALN-AS1 led to rapid, dose-dependent, and long-lasting knockdown of the ALAS1 mRNA in the liver of non-human primates, with an ED50 of approximately 1.25 mg/kg. Further, in a rat model of AIP, ALN-AS1 administration at doses as low as 2.5 mg/kg resulted in a complete blunting of phenobarbital-induced production of ALA and PBG, the toxic heme intermediates in AIP. Pre-clinical studies with RNAi therapeutics targeting ALAS1 have been published by Alnylam and collaborators previously (Yasuda et al., Proc Natl Acad Sci USA 2014;111(21):7777-7782).
As per the filed CTA, the Phase 1 trial of ALN-AS1 will be conducted in three parts. Parts A and B will be randomized (3:1, drug:placebo), single-blind, single-dose (Part A) and multi-dose (Part B), dose-escalation studies, designed to enroll up to a total of 40 ASHE subjects. The primary objective of Part A and Part B is to evaluate safety and tolerability of single and multiple subcutaneous doses of ALN-AS1. Secondary objectives include evaluation of clinical activity for ALN-AS1 as measured by reduction in plasma and urinary levels of ALA and PBG. Part C will be an open-label, multi-dose study in up to eight AIP patients who experience recurrent porphyria attacks, and will assess safety, tolerability, PK/PD, and clinical activity of multiple doses of ALN-AS1. In addition, this part of the study will include an exploratory evaluation of the effects of ALN-AS1 on the number and severity of attacks and other disease symptoms, use of hematin and pain medications, number and duration of hospitalizations, and quality of life.
"Patients afflicted with acute hepatic porphyrias, such as AIP, can suffer from severe and recurrent attacks that are potentially life-threatening and that can result in a markedly decreased ability to lead a normal functioning life. Current treatment options are limited, especially for patients with recurrent attacks that often require monthly hospitalizations for administration of hematin and pain management," said Desiree LyonCo-Founder and Executive Director of the American Porphyria Foundation. "Today is an important step forward for our patient community, as ALN-AS1, a promising investigational medicine for the treatment of acute hepatic porphyrias, has entered clinical testing. I am so pleased with Alnylam's commitment to make a difference in the lives of our patients."
In addition to the Phase 1 trial, Alnylam and clinicians from the American Porphyria Consortium and The European Porphyria Network are currently enrolling patients in the EXPLORE trial, a prospective observational study of patients with acute hepatic porphyrias - including AIP, variegate porphyria, and hereditary coproporphyria - suffering from recurrent attacks. With this study, Alnylam and clinical investigators aim to learn more about the clinical course, management, and disease burden of patients with acute hepatic porphyrias that suffer from recurrent attacks.
In January 2014, Alnylam and Genzyme, a Sanofi company, formed an alliance to accelerate and expand the development and commercialization of RNAi therapeutics across the world. The alliance is structured as a multi-product geographic alliance in the field of rare diseases. Alnylam retains product rights inNorth America and Western Europe, while Genzyme obtained the right to access certain programs in Alnylam's current and future Genetic Medicines pipeline, including ALN-AS1, in the rest of the world. In certain defined instances, Genzyme has co-development/co-commercialization and/or global product rights. Genzyme's rights are structured as an opt-in that is triggered upon achievement of human proof-of-principle.
About ALN-AS1
Alnylam is developing ALN-AS1, a subcutaneously administered, investigational RNAi therapeutic targeting aminolevulinic acid synthase 1 (ALAS1) for the treatment of acute hepatic porphyrias, including acute intermittent porphyria (AIP). AIP is an ultra-rare autosomal dominant disease caused by loss of function mutations in porphobilinogen deaminase (PBGD), an enzyme in the heme biosynthesis pathway that can result in accumulation of toxic heme intermediates, including aminolevulinic acid (ALA) and porphobilinogen (PBG). Patients with AIP can suffer from acute and/or recurrent life-threatening attacks characterized by severe abdominal pain, neuropathy (affecting the central, peripheral or autonomic nervous system), and neuropsychiatric manifestations. ALN-AS1 is an ESC-GalNAc-siRNA conjugate targeting ALAS1, a liver-expressed, rate-limiting enzyme upstream of PBGD in the heme biosynthesis pathway. Inhibition of ALAS1 is known to reduce the accumulation of heme intermediates that cause the clinical manifestations of AIP. ALN-AS1 has the potential to be a prophylactic approach for the prevention of recurrent attacks, as well as for the treatment of acute porphyria attacks.
About Acute Hepatic Porphyrias
The porphyrias are a family of rare metabolic disorders with autosomal dominant inheritance predominately caused by a genetic mutation in one of the eight enzymes responsible for heme biosynthesis. Acute hepatic porphyrias constitute a subset where the enzyme deficiency occurs within the liver, and includes acute intermittent porphyria (AIP), hereditary coproporphyria, and variegate porphyria. Exposure of acute hepatic porphyria patients to certain drugs, dieting, or hormonal changes can trigger strong induction of aminolevulinic acid synthase 1 (ALAS1), another enzyme in the heme biosynthesis pathway, which can lead to accumulation of heme intermediates that precipitate disease symptoms. Patients with one of the acute hepatic porphyrias can suffer from a range of symptoms that, depending on the specific type, can include acute and/or recurrent life-threatening attacks with severe abdominal pain, peripheral and autonomic neuropathy, neuropsychiatric manifestations, cutaneous lesions and possibly death if untreated or if there are delays in treatment. The only approved treatment for acute attacks is hematin (Panhematin® or Normosang®), a preparation of heme derived from human blood. Hematin requires administration through a large vein or a central intravenous line and is associated with a number of complications including thrombophlebitis or coagulation abnormalities. While hematin is not approved for prophylactic use (i.e., the prevention of acute attacks), it is often used in this manner in patients who experience recurrent attacks. Chronic administration of hematin has been found to result in renal insufficiency, iron overload, systemic infections (due to the requirement for central venous access) and, in some instances, tachyphylaxis.
About RNAi
RNAi (RNA interference) is a revolution in biology, representing a breakthrough in understanding how genes are turned on and off in cells, and a completely new approach to drug discovery and development. Its discovery has been heralded as "a major scientific breakthrough that happens once every decade or so," and represents one of the most promising and rapidly advancing frontiers in biology and drug discovery today which was awarded the 2006 Nobel Prize for Physiology or Medicine. RNAi is a natural process of gene silencing that occurs in organisms ranging from plants to mammals. By harnessing the natural biological process of RNAi occurring in our cells, the creation of a major new class of medicines, known as RNAi therapeutics, is on the horizon. Small interfering RNA (siRNA), the molecules that mediate RNAi and comprise Alnylam's RNAi therapeutic platform, target the cause of diseases by potently silencing specific mRNAs, thereby preventing disease-causing proteins from being made. RNAi therapeutics have the potential to treat disease and help patients in a fundamentally new way.
About Alnylam Pharmaceuticals
Alnylam is a biopharmaceutical company developing novel therapeutics based on RNA interference, or RNAi. The company is leading the translation of RNAi as a new class of innovative medicines. Alnylam's pipeline of investigational RNAi therapeutics is focused in 3 Strategic Therapeutic Areas (STArs): Genetic Medicines, with a broad pipeline of RNAi therapeutics for the treatment of rare diseases; Cardio-Metabolic Disease, with a pipeline of RNAi therapeutics toward genetically validated, liver-expressed disease targets for unmet needs in cardiovascular and metabolic diseases; and Hepatic Infectious Disease, with a pipeline of RNAi therapeutics that address the major global health challenges of hepatic infectious diseases. In early 2015, Alnylam launched its "Alnylam 2020" guidance for the advancement and commercialization of RNAi therapeutics as a whole new class of innovative medicines. Specifically, by the end of 2020, Alnylam expects to achieve a company profile with 3 marketed products, 10 RNAi therapeutic clinical programs - including 4 in late stages of development - across its 3 STArs. The company's demonstrated commitment to RNAi therapeutics has enabled it to form major alliances with leading companies including Merck, Medtronic, Novartis, Biogen, Roche, Takeda, Kyowa Hakko Kirin, Cubist, GlaxoSmithKline, Ascletis, Monsanto, The Medicines Company, and Genzyme, a Sanofi company. In addition, Alnylam holds an equity position in Regulus Therapeutics Inc., a company focused on discovery, development, and commercialization of microRNA therapeutics. Alnylam scientists and collaborators have published their research on RNAi therapeutics in over 200 peer-reviewed papers, including many in the world's top scientific journals such as Nature, Nature Medicine, Nature Biotechnology, Cell, New England Journal of Medicine, and The Lancet. Founded in 2002, Alnylam maintains headquarters in Cambridge, Massachusetts. For more information about Alnylam's pipeline of investigational RNAi therapeutics, please visit
Alnylam Forward-Looking Statements
Various statements in this release concerning Alnylam's future expectations, plans and prospects, including without limitation, Alnylam's views with respect to the potential for RNAi therapeutics, including ALN-AS1 for the treatment of acute hepatic porphyrias, its expectations regarding the reporting of data from its ALN-AS1 clinical studies, its expectations regarding the potential market opportunity for ALN-AS1, its expectations regarding its STAr pipeline growth strategy, and its plans regarding commercialization of RNAi therapeutics, constitute forward-looking statements for the purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including, without limitation, Alnylam's ability to discover and develop novel drug candidates and delivery approaches, successfully demonstrate the efficacy and safety of its drug candidates, the pre-clinical and clinical results for its product candidates, which may not be replicated or continue to occur in other subjects or in additional studies or otherwise support further development of product candidates, actions of regulatory agencies, which may affect the initiation, timing and progress of clinical trials, obtaining, maintaining and protecting intellectual property, Alnylam's ability to enforce its patents against infringers and defend its patent portfolio against challenges from third parties, obtaining regulatory approval for products, competition from others using technology similar to Alnylam's and others developing products for similar uses, Alnylam's ability to manage operating expenses, Alnylam's ability to obtain additional funding to support its business activities and establish and maintain strategic business alliances and new business initiatives, Alnylam's dependence on third parties for development, manufacture, marketing, sales and distribution of products, the outcome of litigation, and unexpected expenditures, as well as those risks more fully discussed in the "Risk Factors" filed with Alnylam's most recent Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) and in other filings that Alnylam makes with the SEC. In addition, any forward-looking statements represent Alnylam's views only as of today and should not be relied upon as representing its views as of any subsequent date. Alnylam explicitly disclaims any obligation to update any forward-looking statements.
                               "Remember....Research is the key to your cure!"

Wednesday, June 24, 2015

What is Variegate Porphyria?

What is VP?

Variegate Porphyria (VP)

This form of hepatic Porphyria is most common in South Africans of Dutch ancestry. It is relatively uncommon elsewhere. It is an autosomal dominant disorder and may produce acute attacks (as in AIP) as well as chronic skin photosensitivity. The deficient enzyme is protoporphyrinogen oxidase. In acute attacks, urine PBG is increased as in AIP. Diagnosis of latent carriers is made by finding excess coproporphyrin in urine and both coproporphyrin and protoporphyrin in feces, or by DNA mutation analysis (see AIP). The most sensitive screening test for VP is probably a plasma porphyrin assay. In patients with skin manifestations, it is important to distinguish VP or HCP from PCT, because treatment by phlebotomy or low-dose chloroquine is ineffective in VP and HCP. Acute attacks are managed and may be prevented as in AIP.

To learn more please visit or call 1-866-APF-3635 for a comprehensive Dr. Kit or Patient kit sent out to you.

                      "Remember....Research is the key to your cure!"

Monday, June 22, 2015

Tony Mc Laughlins fight with VP from the UK

Hi my name is Tony McLaughlin I'm 52 and from Yorkshire in the UK but now live in Galway Ireland. 

I was diagnosed in 1993 with VP, after my sister found out she had VP, my sister went to see a cardiologist on an unrelated matter and the cardiologist recognized the skin symptoms which given it's rarity was a lucky break and they tested the rest of the family.

 I have 2 grown daughters one was also diagnosed through genetic testing as having VP but she's 24 with no symptoms, although she has to be careful with unsafe drugs and the sun.

Since 1993 I was relatively stable apart from fragile skin in the summer,  that was until 2010 when I had a severe attack exacerbated by dithering doctors who didn't believe all my symptoms were due to Porphyria and kept treating me for other things until my wife stepped in and read them the riot act, they quickly changed their tune and handed me over to a different team who got the Heam Arginate for the UK (in USA Panhematin) and saved my life, but because of the delay I'd developed all sorts of symptoms that took time to sort themselves out.

 Since then I've had 5 more attacks but I recognize the symptoms early got myself to the hospital and have been treated with Heam every time.
All of my attacks have been caused by pain from other conditions notably Kidney stones and back pain, hopefully if we can stop the triggers we can stop provoking my attacks. 

Tony McLaughlin

                           "Remember....Research is the key to your cure!"

Wednesday, June 17, 2015

The Girl Who Mewed


The Girl Who Mewed

By Robert Marion|Tuesday, August 01, 1995
Mrs. Ludlow was an attractive woman in her mid-thirties, but she looked as if she could use a good night’s sleep. Her nine-year-old daughter sat at her side. After introducing myself, I led them into my office and asked Mrs. Ludlow if she knew why she needed to see me. Well, to tell you the truth, no, she said, sighing. We’re here because the Committee on Special Education at our elementary school said they need a report from you.

Why is your daughter being evaluated?

Nicole’s a bright kid, but she’s missed so much school this year that she’s failing third grade. They’re trying to decide whether to give her home tutoring, put her in special ed, or make her repeat the year. So they want to find out why she has these attacks. But frankly, Nicole’s already been seen by more than a dozen specialists. So far, no one’s been able to tell me what’s wrong with her.

While Mrs. Ludlow spoke, her daughter sat stone still on a chair across from her, staring into space.

Well, I’m a medical geneticist, I explained. I take care of children with birth defects and inherited diseases. Is there any reason to think Nicole’s condition is inherited?

Not that I know of.

Well, if it’s all right with you, I’ll begin by asking some questions about Nicole’s past; then I’ll examine her. Then we’ll talk about where we go from there. Okay?

She nodded her head.

Let’s start at the beginning, I said. How much did Nicole weigh at birth? As the words were coming out of my mouth, the child began to make a strange mewing noise. It sounded like a cat stuck in a closet. The noise came from somewhere deep inside the girl’s throat, not her vocal cords exactly but from somewhere farther down. After finishing my question, I gazed at Nicole, trying to figure out what she was trying to say.

Quiet, the girl’s mother said. Don’t make that noise. That’s a bad noise.

Nicole, still staring off into space, immediately became quiet.

She’s usually a nice, sweet kid, said Mrs. Ludlow apologetically. But she’s having one of her attacks. The attacks are the problem.

I stared at the little girl, trying to get her attention. Although she looked fine, she behaved as if she were in a world of her own. Never did she make eye contact with me; not once did she even look my way.

Has anyone suggested that Nicole might be autistic? I asked.

No. She’s usually very outgoing. It’s only during her attacks that she acts this way. Can autism come and go like this?

I shook my head. To say this girl had grabbed my attention was an understatement. How often does this happen?

A couple times a year. Actually, it’s good you’re seeing her today, so you can understand what I’m talking about. When she’s her normal self and I try to explain what’s wrong with her, people usually think I’m crazy.

How long does this last? I asked, though I wasn’t sure what this actually referred to.

Can’t be sure, the mother replied. Sometimes it’s just a day or two. The longest has been nearly four weeks. And nothing seems to bring them on. They just seem to come and go.

Are they seizures? I asked.

That’s what the neurologists have always thought. Over the years, Nicole’s been seen by five neurologists. She’s been hospitalized three times for overnight brain-wave tests. She’s had two CT scans, an MRI, and about a hundred blood tests. Every test has turned out perfectly fine. Every doctor has told me that he could find nothing wrong with my daughter. Some have even accused me of making the whole thing up. But look at her-- you can verify I’m not making this up, can’t you?

I said yes, I’d certainly be willing to swear in a court of law that she hadn’t invented Nicole’s illness. You seem to know a lot about medicine, I commented. Do you have a medical background?

No, she replied. But what I’ve gone through with this kid has been a medical education.

Has anyone tried to treat these episodes with medication?

Sure, she responded without hesitation. Every neurologist has started Nicole on some form of antiseizure medication. Just last week the doctor we saw put her on Tegretol. None has done a bit of good. Some, if you ask me, have actually made her worse.

How old was Nicole when the episodes started? I asked, still groping in the dark.

As Mrs. Ludlow told her daughter’s story, the look of exhaustion lifted from her face. She explained that Nicole had been perfectly healthy until she was three and had surgery on an elbow she’d fractured in a fall. But after the operation, she just never woke up from the anesthesia. It was terrifying--she went into a coma and nobody could bring her out of it. At first they thought she’d suffered brain damage. They did a CT scan, but it was normal. They gave her all kinds of medications, antibiotics, steroids, but Nicole just wouldn’t wake up. I was sure she was going to die.

I thought for a minute, trying to understand the relationship between the anesthesia and the onset of the illness. In the back of my mind, a distant bell began to ring. The story was starting to remind me of something. How long did she stay like that?

Two weeks. For two weeks I sat at her bedside, holding her hand, talking to her, trying to wake her up. The doctors kept telling me they couldn’t find anything wrong. Then one day she just woke up. She opened her eyes, looked at me and said, ‘Hi, Mommy,’ and that was it.

While her mother was talking, Nicole got up and walked over to my filing cabinet. She placed her face against the cabinet’s metal front and stood there, as rigid as a statue. Is she okay?

Mrs. Ludlow shrugged. I guess so. As all right as she ever gets during one of her attacks.

So after that first episode, was she back to her old self?

It was as if nothing had happened, she said, except that the right side of her face drooped. The neurologist told me she had facial palsy and that she might have it for the rest of her life. Of course, he was wrong--the doctors have been wrong about everything about Nicole. The droopiness lasted about a week. But since then it’s come back a few times, usually during or right after an attack.

On the pad on my desk, I wrote Coma after anesthesia and beneath it Recurrent facial palsy. The bell inside my head was ringing louder now. So how many of these attacks has Nicole had?

Mrs. Ludlow paused and sighed. Somewhere between 20 and 25.

Other than the coma and the facial palsy, I continued, what other problems have occurred during the episodes?

Let’s see, Mrs. Ludlow said. Sometimes her speech gets slurred, as if she’s had a stroke. The bell in my head was ringing even louder now. I wrote the words Slurring of speech on the pad. And insomnia, she added. That’s the worst part. Nicole can go four or five days in a row without sleeping. And of course I have to stay awake, too, because I’m afraid she might hurt herself.

I wrote Insomnia on the next line of the pad. Undoubtedly this was the cause of Mrs. Ludlow’s haggard appearance. Anything else?

Yes, she gets bad pains in her neck, her chest, and her belly. Once I thought she was having a heart attack. Another time the doctors in the emergency room wanted to take her appendix out.

As I wrote Pain on the pad, I thought I finally knew what was wrong with Nicole. I just needed one more bit of information to confirm my suspicion. During these attacks, is there anything unusual about Nicole’s urine?

You’re the first person ever to ask, but there is something. When she’s sick, Nicole’s urine gets very dark. Does that mean anything?

It sure did. By now the bells in my head were sounding an alarm. I was almost positive that Nicole had a disorder called acute intermittent porphyria, or AIP.

Much as I hate to admit it, my flash of diagnostic insight wasn’t the result of my being smarter than the dozen other doctors who’d seen Nicole. I hadn’t read more articles, I didn’t have better clinical acumen, and I hadn’t asked more-probing questions. The explanation for my medical epiphany was simple.

In the weeks prior to the Ludlows’ visit, I was at work on a book about historical figures who were afflicted with genetic diseases. Just the month before, I’d finished a chapter on King George III, the English monarch at the time of the American Revolution. Throughout his reign, King George suffered a series of mysterious--and ultimately incapacitating-- illnesses. Just like Nicole’s, his attacks came and went without warning. His symptoms--nervous trembling, altered consciousness, intractable pain, and terrible insomnia--mystified doctors. In 1966 two British psychiatrists finally proposed a logical explanation for King George’s ailment. Based on a study of the records kept by the king’s personal physician, they suspected that King George had probably suffered from porphyria.

The porphyrias are a group of rare inherited disorders that affect the body’s ability to make hemoglobin, the molecule that enables red blood cells to absorb and release oxygen. Heme is the iron-containing portion of hemoglobin, and patients with porphyria don’t make one of the several enzymes needed to make normal amounts of it. As a result, many patients with porphyria have two symptoms in common. First, they are anemic because they cannot make enough heme. Second, because heme is not being assembled properly, the precursors of heme build up in the blood. The accumulation of these chemicals, which are toxic to the skin, the liver, and the nervous system, can cause an array of other puzzling symptoms.

The form of porphyria that affected George III, however, does not cause constant symptoms. Under normal circumstances, there is enough enzyme to maintain good health. But during illness or emotional stress, or following exposure to certain drugs or chemicals, patients can experience unexplained aches and bizarre neurological disturbances. And because of the buildup of heme precursors, they excrete abnormally dark urine.

Nicole’s first attack had followed exposure to anesthetic agents, some of which are known to exacerbate symptoms. In the following years, she had been treated with the anticonvulsant phenobarbital, which also makes symptoms worse. In fact, the attack that was at that moment gripping Nicole may well have been brought on by treatment with the anticonvulsant drug she’d begun to take the week before.

The more I thought about it, the more convinced I became that Nicole had AIP. Although the condition rarely causes symptoms in young children, the resemblance between her symptoms and King George’s was too striking for mere coincidence. To prove the diagnosis, though, I had to complete two tasks. First, since AIP is inherited when a gene is passed from an affected parent to a child, I had to find out which of Nicole’s parents also suffered from the disease. And second, I had to prove that Nicole’s blood bore evidence of the biochemical abnormality that causes AIP. I turned my attention to the first of these tasks.

I told Mrs. Ludlow that Nicole’s dark urine might be significant and continued with my questioning. How was your pregnancy with Nicole?

Awful, Mrs. Ludlow replied. I was hospitalized twice. The first time, I was in my sixth week. I began having terrible belly pain. My doctor operated to see what was going on.

Did he find anything wrong?

No, that’s the strange part: everything was fine. Then about a week later, the pain just went away. Weird.

I was ready to burst. Mrs. Ludlow’s unexplained pain was most likely an attack of porphyria. I kept probing. When was the second hospitalization?

A month later. It was terrible. I was vomiting so much I was hospitalized for six weeks for dehydration.

Again, these symptoms were consistent with porphyria. The stress of pregnancy could have triggered the attacks. Have you ever had any episodes like Nicole’s? I asked. Mrs. Ludlow shook her head.

When I asked about the rest of the family, Mrs. Ludlow said that her husband and his family were in excellent health, but members of her side of the family had had a series of unexplained health problems. My mother’s okay, she said, but my father’s a mess. People think he’s a drunk because he has blackouts, but I know he never takes a drink--it makes him sick to his stomach. And then, his older sister has had seizures all her life..

Anything besides seizures? I asked.

She shook her head. That sister has a daughter who’s okay...

That would be your first cousin?

Yes, she’s okay, but her daughter has some rare disease. I don’t know what it’s called.

Porphyria? I asked, nearly jumping out of my skin.

Mrs. Ludlow’s eyes opened wide. Yes, that’s it. How did you know?

Mrs. Ludlow, I’ve been thinking for the past few minutes that porphyria would explain all of Nicole’s problems. Since it’s an inherited condition, I’ve been waiting for you to tell me that someone else in your family has it.

She seemed mystified. But how can my cousin and I both have daughters with it if nobody else in the family has it? she asked dubiously.

Well, Nicole and your cousin’s daughter aren’t the only ones who have it. I’m pretty sure those problems you had during your pregnancy were episodes of porphyria. And your father’s blackouts and his inability to tolerate alcohol? Those are probably also caused by porphyria.

What about my cousin? Mrs. Ludlow asked. She’s never been sick...

That’s what’s strange about this disease, I interrupted. It varies widely from one person to the next. Some people are sick all the time, others never have a sick day in their lives. I can’t explain it better than that.

Mrs. Ludlow considered this. If she really does have porphyria, and I’m not sure she does, what can we do?

Well, we can’t cure it, but we can do a lot to help her. I explained that putting Nicole on a high-carbohydrate diet and keeping her off certain medications could prevent the attacks. The first step would be to take Nicole off Tegretol. I also explained that I needed samples of blood and urine from Nicole to confirm the diagnosis. I then asked if Mrs. Ludlow had any more questions.

Just one, she said. How were you able to make this diagnosis when so many other doctors didn’t think of it?

I just shrugged. What I should have told her was that we doctors are just like everyone else. We go to the movies, watch TV, read newspapers and novels. If we happen to see a patient who has symptoms of a rare disease that was featured on the previous night’s Movie of the Week, we’re more likely to consider that condition when making a diagnosis.

Blood tests ultimately confirmed my diagnosis of acute intermittent porphyria in Nicole Ludlow and her mother. But I didn’t make the diagnosis because I’m a brilliant diagnostician or because I’m a sensitive listener. Had I seen Nicole one year before, I’m sure I would have failed. No, I succeeded where others failed simply because the Ludlows and I managed to run into each other in exactly the right place, at exactly the right time.

              "Remember....Research is the key to your cure!"

Monday, June 15, 2015

The story of Kristen Elizabeth Harris and Porphyria

My name is Kristen.  I have been diagnosed of Porphyria since I was 7 years old. This is now 11 years ago roughly. The doctors did not know what was wrong with me. They were doing ever imaginable test and kept referring me and my mother back out to so many other different specialists. The tests were coming back negative for everything and eventually the did not even believe my mother anymore and assume she was making everything up. There was a doctor in the Bronx, New York, Doctor Robert Marion at Montefiore Hospital. He was a new doctor and just studied the signs of Porphyria. After questioning my mother on the medications I was on and my symptoms he realized what I did have. My mother knew that there was some weird rare disease that her father and others in her family had but, could not remember it.  Finally after Doctor Marion asked questions and said the name she confirmed that is what our family had and my grandfather died of. 

I started associating with the  American Porphyria Foundation in 2003 at the age of 16. 

     Thanks to Desiree Lyon and Yvette Strange I have been able to fight this. I still go through my trials and have to go in and out of the hospital for treatments. "The American Porphyria Foundation has guided my emergency room doctors on how to properly care for me not just emergency room, but also in accordance to what I believe in religiously with my conscience." 

There is a song by Melissa Etheridge called I run for life. There is a verse says, "And they cut into my skin and they cut into my body but they will never get a piece of my sole." 

No matter what the doctors do I will always have my sole and my faith in Jehovah God no matter what this disorder brings. This is my story of Porphyria.  

             Stay tuned for the next blog from Discovery magazine on the Girl who Mewed!

                             "Remember....Research is the key to your cure!"

Friday, June 12, 2015

NBC June 14th on EPP- Explanation from APF

Please be Sure to check out " Out of the Shadows"  experiences of people who have EPP.  The date it will air is Sunday June 14th 2015.  Please check your local NBC stations for times.

     You may ask though what exactly is EPP Porphyria?  Please feel free to read more about this explanation this information comes directly from the APF.

Erythropoietic Protoporphyria (EPP) or Protoporphyria

Erythropoietic Protoporphyria (EPP) or Protoporphyria
Erythropoietic Protoporphyria is characterized by abnormally elevated levels of protoporphyrin IX in erythrocytes (red blood cells) and plasma (the fluid portion of circulating blood), and by sensitivity to visible light that is usually noticed in early childhood and occurs throughout life.  EPP can result either from mutations of the ferrochelatase gene (FECH), or less commonly the delta-aminolevulinic acid synthase-2 gene (ALAS2).  When EPP is due to an ALAS2 mutation it is termed X-linked protoporphyria (XLP), because that gene is found on the X chromosome. 
Protoporphyrin accumulates first in the bone marrow in EPP, and then in red blood cells, plasma and sometimes the liver. Protoporphyrin is excreted by the liver into the bile, after which it enters the intestine and is excreted in the feces. It is not soluble in water, so is not excreted in the urine. 
EPP is the third most common type of porphyria, and the most common in childhood.  It causes very painful photosensitivity and can greatly impair quality of life.  Delay in diagnosis is greater than with any other type of porphyria. 
Swelling, burning, itching, and redness of the skin may appear during or after exposure to sunlight, including sunlight that passes through window glass. This can cause mild to severe burning pain on sun-exposed areas of the skin.  Usually, these symptoms subside in 12 to 24 hours and heal without significant scarring. Blistering and scarring are characteristic of other types of cutaneous porphyria but are unusual in EPP.  Skin manifestations generally begin early childhood and are more severe in the summer.
There is an increased risk of gallstones, which contain protoporphyrin. Excess protoporphyrin can also cause liver damage.  Less than 5% of EPP patients’ severe liver damage and a condition caused protoporphyric hepatopathy that sometimes requires liver transplantation. 
Diagnosis and Genetic Counseling
EPP should be suspected in anyone with non-blistering photosensitivity especially when is it prolonged and beginning in childhood.  It is easy to make a diagnosis, or rule it out, once it is suspected. 
The diagnosis of EPP is established by finding an abnormally high level of total erythrocyte protoporphyrin, and showing that this increase is mostly free protoporphyrin rather than zinc protoporphyrin.  There is considerable confusion about which test to order.  Sometimes laboratories have measured only zinc protoporphyrin and reported results incorrectly as “protoporphyrin” or “free erythrocyte protoporphyrin (FEP)”.  Laboratories that measure total erythrocyte protoporphyrin, free protoporphyrin and zinc protoporphyrin and report results reliably are:
  • Porphyria Laboratory and Center, University of Texas Medical Branch at Galveston, 1-409-772-4661
  • Mayo Medical Laboratories, 1-800-533-1710 
  • ARUP Laboratories

Porphyrins are almost always elevated in plasma in EPP, but may be normal in mild cases.  Fecal porphyrins may be normal or increased. 
An experienced biochemical laboratory can usually distinguish between patients with EPP and XLP, because the former have much less zinc protoporphyrin in their erythrocytes.  This can be explained because in the marrow the enzyme ferrochelatase not only normally makes heme (iron protoporphyrin) from protoporphyrin and iron, but can also make zinc protoporphyrin, especially when excess protoporphyrin is present or iron is deficient.  However, this does not replace DNA studies. 
Rarely, EPP develops in adults in the presence of a bone marrow disorder such as polycythemia vera, and is due to expansion of a clone of red blood cell precursors in the marrow that is deficient in ferrochelase. 
DNA studies are important for confirming the diagnosis of EPP and XLP and for genetic counseling.  This should be completed first in a person known to have the disease, and the information about the mutations in that individual used to guide testing of family members. 
When EPP is due to a FECH mutation the inheritance is described as autosomal recessive.  It is most common to find that one severe mutation is inherited from one parent and another weak mutation inherited from the other parent.  The weak mutation is quite common in normal Caucasians, rare in Blacks and even more common in Japanese and Chinese populations.  This mutation is sometime referred to as “hypomorphic” because it results in formation of a less than normal amount of ferrochelatase.  But is does not cause EPP unless it is paired with a severe mutation.  The severe mutation is characteristic for an EPP family and is present in all affected individuals.  “Carriers” of the severe mutation are not affected because they do not have the weak mutation.  Affected individuals and unaffected carriers can transmit the severe mutation to the next generation.  Some of their children will have EPP if the other parent has a copy of the weak mutation.  Rarely, the weak mutation is absent in an EPP family and two severe mutations are found, with at least one producing some ferrochelatase. 
In XLP, mutations of the ALAS2 gene, which is found on the X chromosome, causes an increase in the production of the enzyme ALAS2 in the bone marrow.  Several of these “gain of function” mutations have been described in different XLP families.  In XLP protoporphyrin production exceeds that needed for heme and hemoglobin formation.  Like hemophilia and other X linked genetic diseases, XLP is more common in men.  Women have two X chromosomes and are usually not affected because they have a normal as well as a mutated ALAS2 gene.  Men have only one X chromosome and will be affected if they inherit an ALAS2 mutation.  Women with an ALAS2mutation will, on average, pass that mutation to half of their daughters (who will usually be unaffected carriers) and to half of their sons (who will be affected). 
Treatment and Management
1.  Sunlight protection
Protection from sunlight is the mainstay of management of EPP, and this is necessary throughout life.  Disease severity and porphyrin levels in erythrocytes and plasma probably remain high and relatively constant throughout life in EPP.  However, this has been little studied and more longitudinal observations are needed.  Life style, employment, travel and recreation require adjustment in order to avoid painful reactions to sunlight and even from exposure to fluorescent lighting.  For these reasons EPP can substantially affect quality of life. 
Protective clothing, including broad-brimmed hats, long sleeves, gloves and trousers (rather than shorts), is beneficial.  Several manufacturers specialize on clothing made of closely woven fabrics for people with photosensitivity. 
2.  Beta-Carotene (Lumitene Tishcon)
Beta-carotene is an over the counter product that was originally developed in a purified form as a drug for the treatment of EPP, and was shown to be effective by Dr. Micheline Mathews-Roth at Harvard University and others.  The pharmaceutical grade formulation is now distributed by Tishcon as Lumitene, and can be ordered by calling 1-800-866-0978 or via the website  Other products are less standardized and reliable and are not recommended. 
Beta-carotene provides protection by quenching reactive oxygen products that form when protoporphyrin is activated in the skin by light.  It is important to take an amount that is adequate to be protective.  For more information about Lumitene, including a recommended dosing schedule, please see the Lumitene section of this website.

3.  Other considerations
In an occasional patient, protoporphyrin causes liver problems, so monitoring liver function is important. EPP patients should also not use any drug or anesthetic which causes cholestasis (slowing down bile flow), and should also avoid alcohol. Women should avoid medications containing estrogen (birth-control pills, hormone replacement therapy), and men should avoid testosterone supplements, as these substances can also have deleterious effects on the liver of a person with EPP.
Consult a specialist.  Because EPP is a rare condition, most physicians are not knowledgeable about it.  Contact The American Porphyria Foundation, 713-266-9617 for contact with an expert and to provide further information.  A Medic Alert bracelet with instructions to contact a specialist if needed is a worthwhile precaution.
Yearly monitoring.  Testing to include erythrocyte total protoporphyrin, plasma porphyrin, complete blood counts, ferritin and liver function tests should be done yearly.  Porphyry levels are expected to be stable and liver tests to remain normal.  EPP patients may have evidence of iron deficiency, and an iron supplement may be advisable if the serum ferritin is below about 20 ng/mL. 
Vitamin D.  Because they avoid sunlight, EPP patients are likely to be deficient in vitamin D.  A vitamin D supplement with calcium is recommended for bone health. 
Liver protection.  It is important to avoid other causes of liver disease that might promote the development of liver complications from EPP.  Patients should avoid alcohol and other substances that might damage the liver, including many herbal preparations, and be vaccinated for hepatitis A and B. 
Surgical lights. Strong operating room lights can cause photosensitivity of the skin and even surfaces of internal organs.  Flexible membrane filters, such as CL5-200-X from Madico Co., are available to cover surgical lights and offer some protection.  This is especially important in EPP patients with liver failure, which causes even greater increases in protoporphyrin levels and photosensitivity. 
Drugs.  Drugs that are harmful in other porphyrias are not known to make EPP worse, but are best avoided as a precaution.  This may include estrogens and other drugs that might reduce bile formation.  A short course of a non-steroidal anti-inflammatory drug can provide some pain relief after an episode of photosensitivity, but can cause ulcerations of the digestive track especially with prolonged use. 
Laser treatment.  According to Dr. Roth, laser treatments for hair removal or eye surgery have not been a problem in EPP people.  But the doctor should be made aware of the diagnosis, and that laser output between 400 and 650 nanometers might be harmful. Before hair removal treatment, the doctor may irradiate a small area of the skin to be treated for the length of time it will take to do the hair removal to ascertain if the patient would react within the period of time that a reaction to sunlight would be expected in that patient.  
Children with EPP.  Avoiding sunlight can be difficult for children with EPP who have less sunlight tolerance than their friends.  Camp Discovery is an option for such children.  It provides a week-long summer camping experience of fishing, boating, swimming, water skiing, arts and crafts, and just plain fun for young people with skin disorders, and is sponsored by the American Academy of Dermatology.  Full scholarships, including transportation, are provided by the American Academy of Dermatology through generous donations of their members and other organizations. Members of the Academy are asked to recommend candidates for Camp Discovery, so ask your child's doctor about sending your child to Camp Discovery.
Disneyland and Disney World are responsive to people with sun sensitivity. They will provide a pass to enable you to enter attractions without waiting in line in the sun.
Go to "Town Hall" and explain your problem with photosensitivity. You should bring a physician's letter with you as well as an APF brochure explaining the type of Porphyria you have. The staff will ask you some questions about your limitations (e.g., whether or not you can climb stairs) and how many are in your group. Next time you return, be sure to bring the old card with you, as it will only take about half as long to go through the process on your next trip.
Disney World
Proceed to the "Guest Relations" office at any park (Magic Kingdom, EPCOT, etc.) and request the Special Assistance Pass.
Remember to bring a doctor's note and explanation of your condition, because it is not necessarily visible. People on duty may not be familiar with light sensitivity and its consequences.
Research Opportunities
Patients with EPP and XLP can participate in the research through the Porphyrias Consortium.  The American Porphyria Foundation has information on what research protocols are currently open. 
The Porphyrias Consortium is conducting a Longitudinal Study to better define the natural history of the disease.  This study is currently open for enrollment of new patients. 
The Porphyrias Consortium will be starting a pilot study soon on a drug that may lower porphyrin levels in EPP. 
Clinuvel Pharmaceuticals is developing afamelanotide (Scenesse®) for the treatment of EPP.  This drug is given by injection and increases skin pigmentation.  Another study of this drug is expected to open within the next year. 
All patients with porphyria are encouraged to enter the Porphyrias Registry at the Porphyrias Consortium website.  A link to this website is found on the website of the American Porphyria Foundation.  Registration demonstrates to NIH that patients and their families think that research on porphyrias is important.  You can also ask that one of the 6 porphyria center in the Consortium contact you.  
                       "Remember....Research is the key to your cure!"

Wednesday, June 10, 2015

Natalia Nikova Summer Vacation and AIP

It's summer time have you taken a vacation yet? Please read the reminders off a new personal experience from Natalia Nikova

Acute Intermittent Porphyria

Beware of Mountains
My name is Natalia Nikova.  I was born in Russia in St. Petersburg.  I have AIP.
I went through horrible surgeries and sufferings in Russia before I was properly diagnosed.  That happened when I was between 25 and 30 years old.
After that I was receiving capsules of Adenil through the Red Cross for about four years and injecting myself two times a day.  My recovery was very slow but at the age of 39 I started to feel better and I was able to immigrate to the USA with my daughter and my mother.
I managed to change my profession from Choral conductor to a computer programmer to support my family and my porphyria's symptoms almost disappeared. Now I am 63 years old and in August 2004 all of a sudden I had a reminder. I and my husband went to Peru.  I got immediately sick in Cusco from the high altitude but the altitude sickness was greatly aggravated by porphyria. In addition to a headache and shortness of breath I had nausea, high fever, high blood pressure and grazing pain in my stomach. In fact I became so sick that we had to change our entire itinerary and move to lower regions in Peru.  That was not too much fun because I am a bird watcher I was looking forward to go to Colca Canyon to see Andean Condor.  Even after we returned from Peru I was sick for two weeks with general weakness.
I hope that sharing this story will help some people in planning their vacation.
                      "Remember....Research is the key to your cure!"

Monday, June 8, 2015

Longitudinal Study of the Porphyrias

              Longitudinal Study of the Porphyrias

We are looking for patients volunteers for the 7201 Longitudinal Study of the Porphyrias. Participants of this study DON'T have to travel to the research site. All that needed is to answer porphyria-related questionnaire over the phone. You will be working closely with porphyria experts and researchers.  
The purpose of this long-term follow-up study is to provide a better understanding of the natural history of porphyrias, as affected by available therapies, and to aid in developing new forms of treatment.
Volunteering for research is the most important action you can take to change your future health because Research is the Key to Your Cure.  You can be a Medical Hero and join many patients, who gave some of their time to help find important answers leading to new and improved treatments and a cure. 
In order to participate in a study, please contact us at the APF 866-apf-3635.

"Remember....Research is the key to your cure!"

Wednesday, June 3, 2015

True Joy Poem

True Joy

I'll be happy once I've done this certain thing.

We all say this often not realizing what it brings.

We look only to the future for our happiness.

Letting life slip through our fingers in its fullness.

Will we really feel complete when the task is done, 

or look back and see how we missed so much fun?

Self consumed so we can't see anything else, 

hurting those we love as well as ourselves.

So many things around us to be grateful for, 

when seeking for an answer willingly open the door.

So often, others see what's in front of our face, 

but we're too blind to look as we're snared in the race.

What is this life supposed to be about?

Is it money, fortune, fame, or a big house?

When speaking to a man on his dying bed,

none of these answers are what he said.

Family, love, laughter are what we should seek.

These are the precious things right outside your door.

                               "Remember....Research is the key to your cure

What is δ-Aminolevulinic Acid Dehydratase Porphyria (ADP)?

What is δ-Aminolevulinic Acid Dehydratase Porphyria (ADP)? ADP is more severe than the other acute porphyrias and can present in childhoo...