Thank you for your donation to our campaign to cure TPI Df. I am pleased to report that the campaign was successful. Not just a success but an extraordinary success; we received 80 donations from 3 countries and 13 US states totaling more than $52,000 USD, which is more than 140% of our goal.  This is also the largest EngagePitt campaign to date.   Importantly, the campaign has brought together a community of people concerned about TPI Df who are willing to do something to accelerate research into a treatment.  We know we cannot wait for a company to cure this rare disease and your donation has helped us initiate the process of identifying the first ever TPI Df treatment. I have a wonderful team of researchers and collaborators who are as committed as I am to developing the first ever TPI Df treatment.   In fact, we have recently begun screening our first compound libraries for via lead compounds.  Again, I am grateful to all who contributed to this research, as are the parents of the children who are struggling with this disease at this very moment. 

Thank you for doing your part to make a difference. 

Michael

Michael Palladino, PhD

Professor and Vice Chair of Faculty Affairs

Department of Pharmacology & Chemical Biology

University of Pittsburgh School of Medicine

Thank you for your support of our campaign! We are grateful for your generosity. Read our latest testimonials from family members who have experienced TPI Deficiency in their own families.

Testimonial & Message from Thomas’ Parents:

We decided to support this campaign to help our little Thomas, who is 4 years old and who suffers from a very rare genetic disease, the deficit in triose-phosphate isomerase (TPI). This orphan disease affects only a few children in the world. For the genetic mutation that affects Thomas, life expectancy is usually reduced to early childhood or early childhood. This disease is mainly characterized by a degeneration of the central nervous system, which leads, among other things, to severe respiratory problems, the main cause of death linked to TPI deficiency. Thomas also has permanent hemolytic anemia, which means that his red blood cells are malformed and destroy themselves faster than normal. Most of the time, this does not matter because his body compensates by making many more red blood cells than normal. However, sometimes his body “goes out of whack” and it is sometimes necessary to have a blood transfusion in order to help him find a correct hemoglobin level. Thomas has so far been transfused 4 times.

We fight every day to give the best to our little prince so that he has good care, equipment and a house adapted to his motor disability and especially to fully enjoy life by his side. Unfortunately, the disease progresses and Thomas cannot be independent in his daily life. He needs help dressing, eating, washing and getting around. That said, Thomas never complains, he enjoys life and he is the funniest and most smiling little boy in the world! We have shared a few photos of Thomas and his wonderful smile below. 

The diagnosis was a particularly difficult event. We know what it was like when Thomas was 2 years old, after long medical research. At that time, Thomas had been transfused twice, we knew that there was a problem with hemolytic anemia, but no one thought of a degenerative neurological disease because Thomas' development was completely normal. Suffice to say that we fell from above and that our lives changed after this announcement.

At that time, we tried to contact different doctors, researchers and laboratories to make an inventory on this disease. As this is an extremely rare disease, pharmaceutical companies do not and will not begin research. The only current research is done by university researchers thanks to public and private grants. By reading scientific publications and contacting the researchers who had been able to work on this disease, we found a university research team which is active in the United States. In recent years, considerable effort has been made by Dr. Palladino, an American professor, to try to find a cure for this disease. Now, thanks to his work and thanks to the cooperation of families, he has a platform to carry out tests on human cells. Recently, everything is in place to find and validate a compound capable of stabilizing the mutant TPI gene. This research, hopefully, could serve as treatment in the near future.

This is why we decided to create the association “Together against TPI Deficiency” during these last weeks and to launch our own fundraising effort. All donations from this fund will be donated to the University of Pittsburgh for the team of Professor Palladino who is working on this research. We are in the process of creating the association's website on which we will be able to share information on the disease in order to help the next families or current and future researchers. There is currently no site that deals exclusively with this disease.

We encourage you to donate to this important cause and help children just like Thomas in America, Italy, France and elsewhere in the world.

Thank you for your support!

Parent Testimonial from North Carolina:

It's hard for me to remember how it felt when we first realized something serious was wrong with our 10-month-old daughter and no one could tell us what it was or help with a treatment. And then 5 years later to see that the same disease was taking hold of our 2-year-old son was heartbreaking. And still, doctor after doctor could offer no explanation or help.

Our daughter is now 21 and our son is 17. Through genetic testing we learned a few years ago that they have TPI deficiency and found out how fortunate we are to still have our precious kids with us, as this disease often takes a toll that is not survivable.

Dr. Palladino’s studies have explained why their disease is less severe than other patients, nonetheless day-to-day life is a struggle for my children. They are normal cognitively but have physical symptoms similar to those of cerebral palsy. Muscle weakness, spasticity and lack of coordination mean they need power wheelchairs. Dressing, using the bathroom and eating are challenging every day. As our daughter is now an adult, finding a fulfilling job that she can physically do has been difficult.

When I found Dr. Palladino at the University of Pittsburgh was working on better understanding TPI deficiency and looking for a possible treatment, we were so excited. TPI deficiency is incredibly rare and therefore not studied by virtually anyone in the context of mitigation of human disease. The fact that these studies could identify a first ever treatment for this disease gives me hope. Please consider donating to this important campaign.

Sincerely,

A Mom from North Carolina

Grandparents’ Testimonial from Wisconsin:

We have two grandchildren with TPI deficiency. The oldest is 21 and the youngest is 17. This is called a childhood disease, because most children do not survive. Can you imagine being told that your child has a disease and there is no known cure, and research is almost nonexistent? Hopelessness is a horrible feeling.

The last 21 years have been incredibly difficult watching these two children struggle with this disease that has taken the lives of so many children. It breaks our hearts watching them navigate everyday skills and tasks. They are both in electric wheelchairs which limits their independence and choices for jobs. One of the hardest things to deal with is the fact that no one knew what was wrong or how to help them.

We have no idea where our daughter found Dr. Palladino and learned that he was doing research into TPI deficiency. When she and her family realized they could contribute to Dr. Palladino's research, they jumped at the chance. We all have a deep faith and always believed there would be help out there some day. Dr. Palladino's research has given all of us dealing with this terrible disease hope that there will be help for these children. I told my oldest granddaughter that I believed there would be a "cure" for her in her lifetime and I hoped in my lifetime too. “Dr. Palladino will have to hurry because your time is running out,” she chuckled.

We have made a contribution to the Cure TPI Project at the University of Pittsburgh and are grateful that Drs. Palladino and Vogt are working to find a treatment for this horrible disease. Would you please consider making a contribution to this life saving effort?

Loving Grandparents from Wisconsin

Please see the endorsement letter from Dr. Bruce Freeman, Department Chair for Pharmacology & Chemical Biology at the University of Pittsburgh School of Medicine, for the Cure TPI Deficiency campaign pictured below:

Thank you for the generous support of this campaign thus far! We sincerely appreciate your contributions. The following testimonial is from Elena, whose son, Julian, is affected by TPI Deficiency. Elena and Julian live in Russia and are also seeking a cure for the disease. Please read Elena's testimonial and continue to spread the word about this campaign to help kids like Julian.

Translated from Russian below:

Dear friends. My child, Julian, has been sick since birth with a devastating disease, enzyme deficiency in the TPl 1 gene. The disease is insidious and not fully understood. We are not alone in the world with the same enzyme. Families with this disease are becoming more and more. And every family dreams of a medicine and to continue research in this area. After all, our children want to live.

Very good news. there is a scientist Prof. Palladino and also scientists and pharmacologists who want to engage and help and fight and win! A boy is growing who has a chance to win! I ask those who care to make their unbearable contribution to the victory over the diagnosis and the disease. Means are needed to support the project. Believe and hope!

Elena from faraway Russia and her son Julian.

Original text: 

Отзыв родителя

Уважаемые друзья. Мой ребенок  Юлиан болен с рождения разрушительной болезнью  недостаточностью фермента в   TPl 1   гене. Болезнь коварна и до конца не изучена. Мы не одни в мире с такой же энзимопатией.  Семей с такой болезнью становися все больше и больше. И каждая семья мечтает о лекарстве и об продолжении исследования в этой области. Ведь наши дети хотят жить.

Очень хорошая новость ..есть ученый проф.Палладино и еще ученые и фармакологи , которые хотят заниматься и помочь и бороться и победить.!  Растет мальчик у которого есть шанс победить!. Прошу неравнодушных людей внести свой непосильный вклад в победе над диагнозом и болезнью.Нужны средства для поддержания проекта. Верим и надеемся!

Елена из далекой России и ее сын Юлиан.

We developed an HEK TPIE104D-GFP stable knock-in cell line which provides a convenient optical assay of steady state mutant human TPI protein in the context of a human cell. Working with Dr. Vogt in the drug discovery institute we’ve developed an automated optical screening method and tested a panel of inhibitors against proteins known to target mutant TPI for degradation in flies. Consistent with what was discovered in Drosophila, bortezombib, cycoheximide and luminespib all showed a significant increase in TPIE104D-GFP fluorescence, demonstrating that TPIE104D turnover in human cells is similarly regulated as in Drosophila. As expected, all drugs in this class displayed significant toxicity, however, dose-dependent studies revealed luminespib produced the highest fold increase in GFP with the lowest toxicity. Flow cytometry confirmed that the GFP increase observed was from the healthy cells, validating the use of this human TPIE104D-GFP reporter. We also performed a pilot test in 384 well plates using our automated imaging platform and the method met universally accepted HTS standards demonstrating both the viability of this screening methodology and luminespib as a positive control.