Thalagen™: Gene Therapy Treatment for Thalassemia

[Hemanshu]

Dad champions research for rare, little-known conditions

By Agnes Jasinski | Special to the Tribune July 1, 2009 When Patrick Girondi got into trouble with the law as a teenager, he enlisted into the Air Force to get his life on track. When he had few options as a young adult with no high school diploma, he worked his way up from runner to trader at the Chicago Board of Trade. And when his son Rocco was diagnosed with a rare blood disease at age 2, he left trading for the pharmaceutical industry.

Seventeen years later, Girondi believes a breakthrough is near for thalassemia, a disorder afflicting Rocco and about 100,000 newborns worldwide each year, in which insufficient hemoglobin is produced to carry oxygen throughout the body. Thalassemia patients on average survive to their late 20s, Girondi said.

"I promised God a long time ago, 'If you help me with Rocco, I'll do my best to help others,' " he said.

Rocco has a severe form of the disease and must have blood transfusions every three to four weeks and pills that work to deplete the excess iron in his system, a result of the transfusions. A year after his diagnosis, he was hospitalized for 40 days to undergo experimental treatments, a $75,000 cost not covered by insurance, Girondi said.



Girondi, who is from the Bridgeport neighborhood, founded the Chicago-based biotech company Errant Gene Therapeutics (EGT) in 2003, and the company has been working to develop products to treat "orphan diseases" like thalassemia. He splits his time between Chicago and southern Italy, where experimental treatments have been more available as the disease affects more children of Mediterranean descent.

An orphan disease is described by the National Institutes of Health as one with fewer than 200,000 cases nationwide. To promote more funding for treatments for them, Girondi created the Orphans Dream Foundation in 2007. About $35 million has gone into the project, he said, with much of the money coming from parents with children suffering from orphan diseases and his fellow traders.

Girondi has high hopes that the answer to thalassemia lies in a controlled virus developed by Michel Sadelain of Memorial Sloan-Kettering Cancer Center in New York City. The first clinical trials of the resulting drug, which would be produced by EGT, may be tested on the first human patients by the end of this year, Girondi said.

Christopher Ballas, the director of gene therapy with EGT and an assistant research professor at Indiana University's School of Medicine, said the controlled virus will be used as a carrier to deliver what the patients are lacking. If it works, the technique used for thalassemia could be used to treat other orphan diseases, including sickle cell anemia, Ballas said.

"Here we have a chance to really do something that is of major benefit to a lot of folks who might otherwise be overlooked," Ballas said.

Girondi hopes the drug will be available to Rocco within two years, but the process of gaining approval for its use is not easy. Still, he already has passed two major hurdles that exist for orphan diseases: funding and attention for diseases that are so rare that research is often focused elsewhere.

His most rewarding moments come from meeting with parents. Tracy VanHoutan was introduced to Girondi through a mutual friend after VanHoutan found out his son had the rare nervous system disorder Batten disease.

Girondi then introduced VanHoutan to the leading researcher on the disease. While funding has stalled on clinical trials for Batten disease, VanHoutan is grateful.

"In a time when I was lost, after we got the diagnosis, Pat was an incredible resource," VanHoutan said.

Girondi is more modest.

"I'm just the guy in the middle," he said.

[Schelby]

"Thalassemia patients on average survive to their late 20s"


????????

[Narendra]

"Thalassemia patients on average survive to their late 20s"
????????

I think this was like many years ago what people thought.....

Today, thals have reached in their 40s and 50s and living a as normal life as one can get with optimal management.

Sadly, in some parts of the world - people and even some out-of-date doctors still think that thals do NOT have a long life. Some family members do NOT get hope from the doctors (which leads to parents NOT understanding what needs to be done) and that needs to change.

[Schelby]

My sister passed a 44. She had pulmonary hypertension that she knew about for several years but was not having treated. She refused to see the cardiologist. Then she had other complications. From the issues I have been having at 42, I fully believe she had the same thing going on. I have FINALLY been diagnosed with a hypopituitary disorder causing an adrenal insufficiency, and a growth hormone deficiency amongst other hormonal deficiencies. I do not think I would have survived the last few months if my heart was weak. Now that I KNOW what is going on, I realize that I have been having symptoms for YEARS. The stress of loosing my sister last year set it into high gear, which can happen with endocrine disorders.

I am 42. I have been mismanaged since the beginning of time. I would ask questions and tell drs what I think I needed checked from what I had researched online. They would tell me I was fine. They didn't know any better or they didn't want to listen to me. Now I finally have the right team of doctors. THIS is the KEY. We need to have the right doctors who are willing to listen. I thought I was doing the right things for myself. Cardiology appointments yearly, which would have done me NO good if I were to have Thal related issues. I had some episodes of rapid heartbeats and asked if I needed a 24 hour monitor. I was told NO, I am fine. Then I find out I should have been having a yearly 24 hour monitor. I asked my old endocrinologist for years, yes YEARS to test my pituitary function. He told me it was not necessary because pituitary disorders are very uncommon. I told him I had read Thal patients often have pituitary problems due to iron overload. Still, he would NOT draw simple blood tests. I would have never believed this kind of shoddy medical care could happen here in the USA until I experienced it.

I'm 42 and am feeling VERY lucky my heart is not damaged from medical mismanagemnet. My bones are SO weak due to my old hematologist refusing to transfuse me until my HB was 6 or lower. The hormone deficiencies also contributed to the weak bones. I need hip replacements and the doctors don't want to touch me until I strengthen my bones. That could take years. I am in a very bad way because of mismanagement. We need to keep sharing our stories and experiences so that future patients do NOT have to go through these ordeals.

Also, there is new findings that growth hormone deficiencies are fairly common in adult thal patients even those who are well chelated and have normal iron levels. Nothing to do with the pituitary. Could explain why we get so tired and loose interest in things as we age with thal. I was feeling SO exhausted and awful that I had many moments where I felt that if I didn't think about it, I would stop breathing. It was such a HORRIBLE feeling. I have been on growth hormone replacement injections for about 5 weeks now. I feel like a different person. I'm regaining interest in things. I don't feel horribly weak and exhausted anymore. I am regaining muscle mass that I lost even though I don't move around much... I am severely limited due to the hip arthritis and I sit and lay most of the day. I use a cane or walker to get around depending on how far I have to go. I can't do more than about a city block even with the walker. Still, I'm regaining muscle mass. A lot of the issue is the weak muscles and atrophy in my legs. I have been telling numerous doctors that the atrophy in my legs was too much and too fast to only be caused by the arthritis. I told them for a YEAR and A HALF. NOW that I am rebuilding muscle without effort after starting the hormone replacement, they finally believe me. They are looking at me in awe. I feel it should NEVER have come to this. I am really in a mess here. I figure another year or two before I am back to where I was a few years ago... if I EVER get there. I am hopeful. I believe I can fully recover. Still, should have never come to this. Not when I was specifically asking for the right tests I needed and was being brushed off like I was a crazy hypochondriac.

Everyone, get your growth hormone tested. Also, women know that your estrogen being too low will cause major issues with your bone health. Not sure how this works for men with testosterone. Full hormone panels should be drawn every year. Push for it if your doctors don't know this. Even minor deficiencies can make you feel more tired than you should. I say this from experience. What the good is the longer life we all work so hard for if there is no quality in it? It is important to be heard. Please share this with anyone it may benefit.

Late 20's... HA!

I think I'm ranted out now. :)

[Narendra]

Shelby,

Your post shows what a person (patient) himself can do after learning how to manage their condition. I agree with you - the doctor's should learn to hear to their patients and NOT get their patients messed up.

While US should have been one of the best place for treatment, I don't think conditions like thalassemia are that big for them - throwing it back for the doctors to have a keen interest in.

I would again urge all thals to look at the following document created by Oakland Children's Hospital. it will help in their management of thalassemia. http://www.thalassemia.com/documents...2008.final.pdf

[Schelby]

Good idea posting that link her too, Narenda. It is a great booklet of information. I have printed it and given it to many of my doctors who are uninformed on Thalassemia. Most of them thank me and appreciate it. :)

[ashutosht]

GENE THERAPY NEWS UPDATE

Gene Therapy News


As we speak, vector is being made for the first patients. We believe that the vector will be finished and tested by October-November. At that time, the treating doctors will make the decision on when to commence. They may decide to wait until after Christmas.

Remember that the first phase is about 'doing no harm'.
The second phase is about 'efficacy', does it work?
The third phase is about dosaging.

We are hopefully confident that we will see efficacy already within 40 days of dosing the first patient.

We would like to thank the Thalassemia Foundation and Angela Iacono of Italy. We would like to thank the Cooley's Anemia International and Ron Capano. Both of these groups have helped incredibly to keep things moving forward.

I apologize that I have not written an update recently. Things are moving.

A special thanks also to Sam Salman, Charles Columbus, Omar Halaby and Christina Slater... They have joined the team 4 months ago and have quickly become crucial to the project.

It is July, this year I will do no concerts in Italy. I have no performances scheduled in the US. I am instead scrounging for funds. As you know, we need to stay funded.

Anyway... Maybe next summer I will be able to do some concerts in Bangladesh or India or Iran or Pakistan or France or anywhere that you, my family is.

Please send your warmest wishes and prayeres... Downloads help and anyone who can afford to donate... we're here.

Pat Girondi

[Schelby]

Fabulous news!

[ashutosht]

GENE THERAPY TO MAKE HISTORY IN OCTOBER

Dear family member…

I leave for Pavia in the evening. It will be a historic trip.

Your dreams and prayers, your hard earned resources have made the trip possible. A major disease, (thalassemia, my son Rocco and your son Rocco’s gift) will be treated genetically for the first time.

I will not rant about all of the success that has accompanied us though the halls of the FDA and the canals of science. I would like however to thank you for your presence as comrades and mentors.

October is the 17th anniversary of Rocco’s diagnoses. October is the month when the first patient will leave for the US from Italy to be treated. I don’t know who he is but, for me, it is Rocco. The patient will go through the various phases and begin the therapy after these things are finished.

Your company has grown to 17 patents. We will next tackle Sickle Cell Anemia. Everything that we have learned until now will shorten the trip for Sickle Cell.

I will probably spend more and more time in the Mediterranean where there are a hundred thousand patients. I will build here as we have built in the US. As you know we have collaborating centers everywhere from LA to Singapore.

Our new president is paving the way for a business plan that will ensure that the Orphan Diseases are always a consideration and the life of EGT.

May the Orphan Dream be your dream.




Pat Girondi

[parag]

Hi All,

Any Update on this treatment / trial

regards,

Parag

[ashutosht]

"October 7, 2009 - Vector Production almost completed."

Vector production is almost finished we will begin Clinical Trials on the first patients in the first quarter of 2010.

Keep your prayers coming....

Thanks to all -

Pat Girondi

[Azizuddin]

how much is going to be the cost of gene therapy?

[ashutosht]

In one of the mail Pat said it would be cost similar to bonemarrow transplant

[parag]

Hi All,

Any further update on this issue please,

many thanks,

Parag

[sanjay]

Dear narendra,
Info given in http://www.thalassemia.com/documents...2008.final.pdf helped me know many issues.
I am amazed to read about no. of test required.
thanks a ton, kindly keep us updated on all new develpments.
sanjay