The International world patient alliance appointed Yasser daoudian, chief of the board of Directors of the Rare Diseases Foundation of Iran, as a member of the Advisory Board of this organization. This organization is made up of patients and patient advocacy organizations around the world and aims to ensure all patients have access to safe, high quality and affordable healthcare in the world. The union has been trying to present the latest achievements in medical science by holding scientific seminars and conferences. It also holds meetings with specialists and leaders of NGOs to access new medical knowledge and uses their experience to improve the conditions of patients in all parts of the world. The rare foundation of Iran hopes that interactions with international societies will reduce the number of patients and rare diseases in the world and provide new treatment facilities for rare patients by updating information about rare diseases and proper communication with the world’s medical societies.

https://www.worldpatientsalliance.org/advisory-board/

CMTC-OVM is a worldwide non-profit community that aims to improve the quality of life of people suffering from vascular abnormalities (blood vessel abnormalities), such as CMTC, their families, and stimulate scientific research into these disorders.

The Iran Rare Diseases Foundation congratulates all Persian speakers and Iranians around the world on the Eid of Nowruz.Happy Nowruz

It is hoped that with the cooperation of this organization, we will take steps towards the awareness and treatment of such rare diseases and patients.

The 4^TH volume of the Atlas of rare diseases of Iran has been published. The Atlas, which was accomplished with the research of the group of the scientific-research council and the Medical Commission of the foundation of rare diseases of Iran, has examined rare diseases in this field as brain and neurological diseases.

The current Atlas will be made available to scientific centers, researchers, medical students and others in order to obtain the necessary information in the field related to its topic.

It is worth mentioning that the foundation for rare diseases of Iran has previously published the Atlas of rare diseases of Iran in the fields of: rare internal diseases, rare genetic and congenital diseases, as well as rare metabolic diseases.

Other important research projects of the Rare Diseases Foundation of Iran include of publishing the first color Atlas of the Rare Diseases at the international scientific level which was made available to the public in 1391

Drishti Agarwal

December 13, 2023

The European Commission has granted approval to avapritinib (Ayvakyt) to address moderate to severe symptoms in adult patients with indolent systemic mastocytosis (ISM) who are inadequately managed by current symptomatic treatments. This marks the first approved therapy for individuals with the condition in Europe.

ISM is a rare blood disorder characterized by an abnormal build-up of neoplastic mast cells in the bone marrow and other organs, including the skin. It is accompanied by often distressing symptoms like pruritus, flushing, syncope, headache, vomiting, diarrhea, and abdominal pain. It affects around 40,000 individuals in the European Union. 

Avapritinib is a kinase inhibitor that was developed to selectively target the disease’s key driver, the KIT D816V mutation in mast cells.

After the favorable recommendation from the Committee for Medicinal Products for Human Use in November 2023, the European Commission’s decision to approve avapritinib is grounded in data from the PIONEER trial.

The phase 2 trial found significant and clinically relevant benefits from the use of avapritinib plus best supportive care (BSC) medicines in patients with symptomatic ISM. This was true across various efficacy assessments, encompassing both disease symptoms and the burden of pathologic mast cells.

The first part of the trial established the recommended dose of 25 mg once daily. The second part compared avapritinib 25 mg once daily plus BSC against placebo plus BSC in patients with moderate to severe ISM. The third part is an ongoing open-label extension that is evaluating avapritinib 25 mg once daily for up to 5 years.

So far, avapritinib has been found to lead to significant improvements compared with placebo across primary and all pivotal secondary measures, which were evaluated from baseline to 24 weeks (part 2) and has demonstrated intensified efficacy through 48 weeks of treatment (part 3). Overall, 96% of patients receiving avapritinib completed 24 weeks of treatment and opted to cross over to part 3. The detailed results were published in NEJM Evidence.

In part 2, 212 patients with moderate to severe ISM were randomly assigned to receive oral avapritinib 25 mg once daily (n = 141) or placebo (n = 71) across 42 sites in 13 countries. Compared with the placebo group, the avapritinib group had a significantly greater decrease in the total symptom score (TSS; 15.6 vs 9.2 points; P < .003) and showed a significantly higher rate of achieving a 50% or greater reduction in serum tryptase levels (P < .001).

In part 3, for the crossover patients who finished an extra 24 weeks of treatment (n = 26), the average shift in TSS at 48 weeks was -21.4. Approximately 37% experienced reductions of 50% or greater in TSS, and approximately 59% showed a 30% or greater reductions within around 4 months.

Avapritinib was also well-tolerated, presenting a favorable safety profile, with the severity of most reported adverse events categorized as mild. Common adverse events included flushing, edema, increased blood alkaline phosphate, and insomnia.

In Europe, plans are underway for the initial commercial launch in Germany, followed by subsequent market introductions determined by the respective local healthcare technology assessment and reimbursement timelines.

https://www.medscape.com/viewarticle/europe-approves-avapritinib-rare-mast-cell-disease-2023a1000vb3

University at Buffalo research has identified how a misstep in the genesis of a key component of the kidney causes infantile cystinosis, a rare disease that significantly shortens the lifespan of patients. Published Nov. 30 in the International Journal of Molecular Sciences, the work reveals that the mechanisms that cause the disease could be addressed and potentially cured through the genome-editing technique CRISPR. That could make kidney transplants, the most effective treatment currently available for these patients, unnecessary.

Infantile cystinosis, the most common and most severe type of cystinosis, occurs as the result of an accumulation in the body’s cells of cystine, an amino acid. The buildup damages cells throughout the body, especially the kidneys and the eyes. Treatment consists of medications that work to lower the level of cystine in the body, as well as therapies that address the impaired growth of these children due to the inability to properly absorb nutrients. Some children require feeding tubes. Eventually, patients with infantile cystinosis, also called nephropathic cystinosis, will require dialysis and a kidney transplant.

Promise of stem cells

Human-induced pluripotent stem cells (hiPSCs) are stem cells that can differentiate into many different cell types. They hold tremendous potential for studying genetic diseases; the drawback has been that differentiation into certain cell types has been problematic. Such is the case with many cell types found in the kidney.

But a new protocol developed by this research team was successful.

Ramkumar Thiyagarajan, PhD, assistant professor of geriatric studies at the University of Kansas and formerly a postdoctoral fellow at UB, is first author on the paper.

The protocol involved extracting stem cells from a healthy individual and an individual with infantile cystinosis. The researchers developed a culture medium to grow stem cells that included a small number of defined components present in blood, including insulin, specific proteins, growth factors and others. “Conducting the differentiation protocol under these conditions occurred in a timely manner,” says Taub, “we didn’t have to wait for weeks on end, and it occurred in a reproducible manner.”

The researchers were able to efficiently differentiate the hiPSCs into the kidney proximal tubule, the type of nephron in the kidney that is impaired in infantile cystinosis, as well as in other kidney diseases.

“Unlike in other studies, we were able to retain a number of markers in the tubule that are physiologically important in the kidney’s reabsorptive functions,” says Taub. “Although these markers were expressed in both the normal and the cystinosis-derived hiPSCs, the genesis of the tubule was impaired in the cystinosis-derived cells, mimicking what happens in infantile cystinosis.”

A potential cure

That finding means that the CRISPR genome-editing technique could be used to repair the defective genome and potentially cure the disease. “The normal gene can be introduced in the genome of cystinotic hiPSCs, which can then be injected in the kidney to replace the defective proximal tubules of individuals with infantile cystinosis,” Taub says.

“In cystinotic individuals, it is the renal proximal tubule that degenerates, presumably due to programmed cell death,” explains Taub, “so the entire kidney would not need to be replaced. The defective renal proximal tubules of individuals with this disease can be replaced with normal tubules following the introduction of the normal gene into cystinotic hiPSCs obtained from the patient. And because these tubules are from cells derived from the patient, there should be no problem with tissue rejection.”

The findings are applicable to other kidney diseases where the renal proximal tubule is damaged, including acute kidney injury that can lead to chronic kidney disease and renal failure, and can be fatal.

Initial studies will need to be conducted with animal models as well as with in vitro tissue culture cells.

The research was funded by UB’s WNYSTEM and The Cystinosis Research Foundation.

Source:

University at Buffalo

Journal reference:

Thiyagarajan, R & Taub, M. (2023). Studies with Human-Induced Pluripotent Stem Cells Reveal That CTNS Mutations Can Alter Renal Proximal Tubule Differentiation. International Journal of Molecular Sciences. 

doi.org/10.3390/ijms242317004

https://www.news-medical.net/news/20231211.