Two rare diseases, two pieces of good news

Dr. Stephanie Cherqui

Last week saw a flurry of really encouraging reports from projects that CIRM has supported. We blogged about two of them last Wednesday, but here’s another two programs showing promising results.

UC San Diego researcher Dr. Stephanie Cherqui is running a CIRM-funded clinical trial for cystinosis. This is a condition where patients lack the ability to clear an amino acid called cystine from their cells. As the cystine builds up it can lead to multi-organ failure affecting the kidneys, eyes, thyroid, muscle, and pancreas.

Dr. Cherqui uses the patient’s own blood stem cells, that have been genetically corrected in the lab to remove the defective gene that causes the problem. It’s hoped these new cells will help reduce the cystine buildup.

The data presented at the annual meeting of the American Society of Cell and Gene Therapy (ASCGT) focused on the first patient treated with this approach. Six months after being treated the patient is showing positive trends in kidney function. His glomerular filtration rate (a measure of how well the kidneys are working) has risen from 38 (considered a sign of moderate to severe loss of kidney function) to 52 (mild loss of kidney function). In addition, he has not had to take the medication he previously needed to control the disorder, nor has he experienced any serious side effects from the therapy.


Dr. Linda Marban of Capricor

Capricor Therapeutics also had some positive news about its therapy for people with Duchenne’s Muscular Dystrophy (DMD). This is a progressive genetic disorder that slowly destroys the muscles. It affects mostly boys. By their teens many are unable to walk, and most die of heart or lung failure in their 20’s. 

Capricor is using a therapy called CAP-1002, using cells derived from heart stem cells, in the HOPE-2 clinical trial.

In a news release Capricor said 12-month data from the trial showed improvements in heart function, lung function and upper body strength. In contrast, a placebo control group that didn’t get the CAP-1002 treatment saw their condition deteriorate.

Craig McDonald, M.D., the lead investigator on the study, says these results are really encouraging.  “I am incredibly pleased with the outcome of the HOPE-2 trial which demonstrated clinically relevant benefits of CAP-1002 which resulted in measurable improvements in upper limb, cardiac and respiratory function. This is the first clinical trial which shows benefit to patients in advanced stages of DMD for which treatment options are limited.”

You can read the story of Caleb Sizemore, one of the patients treated in the CIRM-funded portion of this trial.

One thought on “Two rare diseases, two pieces of good news

  1. Gene therapy is a treatment by transferring the genetic information to correct any disorder or pathophysiologic state of patients. The advances in molecular genetics has make gene therapy a realistic goal for medication for this century. Several unresolved problems of this technology need to be addressed which becomes a major impediment for widespread of clinical application. Currently, gene therapy is only applicable to most of the common fetal inherited disorders with no effective alternative therapy exists or therapeutic suboptimal by protein-based replacement strategies.

    Theoretically, gene therapy is a kind of therapeutic by transferring of a nomal copy of a single defective gene into defective cells and is highly effective tool to completely cure any diseases. However, current approaches by using viral vectors as gene transfer vectors showed that virus vector has high efficiency of tranduction and expression of transgene in targeted cell. However, most gene therapies with viral transfer vectors are potentially improved survival rates of patients, they are ineffective at achieving complete of cure. Viral transferring vectors pose a series of limitations for clinical application: 1) Different types of viral vector limit the size of heterologues gene can be inserted into recombinant virions. An increase of total length of DNA beyond the limit may decrease the production of recombinant virions. 2)The efficiency of different viral vectors have varying degrees to delivery the therapeutic gene into the target cells. The inability to produce high-titer of recombinant virus has hampered in vivo utility. 3)The stability of recombinant virus determined the durability of therapeutic gene to function in the targeted cell for a certain period of time.

    Current gene therapy on patient with Cystinosis showed that patient’s developed a positive trends in a mild loss of kidney function, no side effects and no medication. This observation indicated a small proportion of patient’s own blood stem cells but not 100% of cells tranfected with recombinant virus was potentially to partially recovery of defective illness. Viral promoter is highly effective to transduce the heterologous gene to a very high levels. This is in contrast to promoter in human cells which is regulated by enhancer and depressor. The regulation of promoter by both regulators enable cell to up-or downregulation of function gene expression to maintain our tissues and organs to function normally. Although, the stability of recombinant virus in targeted cell may yield long-term benefits to patient’s health and well being. However, the consistency and long-term overexpression of function gene in targeted cell pose a high risk of cell transformation and lead to cancer. Thus, patients with long-term gene therapy require consistency of follow up to make sure the safety and efficacy of treatment.

    Another study showed that gene therapy was a powerful tool to partially recovery of heart, lung and upper body strength in patient with Duchene’s Muscular Dystrophy (DM). The patient was treated with CAP-1002 cells derived from heart stem cells in the HOPE-2 clinical trial. Patients showed improvement of function in heart, lung and upper body strength after 1year of treatment . Stem cells are moveable and the used of heart stem cells may trigger the heart stem cells to migrate to the heart and neighbouring tissues and organs surrounding the heart for repairing . Stem cells are remarkable which can interact with growth factors and switch on the necessary gene to develop many different types of mature cells. Evidence proved that heart stem cells have been found to develop mature liver cells in human. Therefore, the small number of recombinant heart stem cells is potentially partially improvement of upper body in DM patients. It is important to note that, patients who are undergoing gene therapy requires constantly follow up to determine the safety and efficacy of therapy. As mentioned before, the regulation of gene expression in virus is not the same to the human.

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