Information

Update on Potential Therapies for Lowe Syndrome and Dents2 - April 2025

Lowe and Dents2 condition is due to DNA variants that cause deficiencies in an enzyme called OCRL1. The deficiency affects the development of the eyes, brain and kidneys. Various drug therapies have been identified that may correct the Lowe condition, that include repurposing FDA/EMA approved drugs, and Gene therapy is now being researched by the Cure Lowe foundation in Denmark. Two pilot clinical trials using two different EMA approved drugs are to be conducted in at the Bambino Gesù hospital in Rome Italy, led by Dr. Franchesca Emma. As part of the UK Lowe Family outreach initiative to prepare for potential clinical trials in the UK, the charity is encouraging and assisting families to collect medical records especially their DNA mutation and to register with the Sanford CoRDS database and Citizen Health that is complimentary to CoRDS, to get all genetic data into one comprehensive database of OCRL mutations for researchers.

Drug Screening and Therapies

Alpelisib: In 2020 Dr. Jennifer Gallop’s lab at the Gurdon institute in Cambridge University UK identified a drug normally prescribed for cancer treatment called Apelisib (Piqray) that has the potential to correct the kidney condition due to Lowe syndrome and Dents2. Pilot clinical trials using Alpelisib are to be conducted in 2025/26 at the Bambino Gesù hospital in Rome Italy, led by Dr. Franchesca Emma.  This project is called the ALPEDENT project and is funded by the Lowe Syndrome Trust (LST), Dent Disease Foundation USA and The Lowe Syndrome Association (LSA) USA.

Piclidenoson: A team led by Dr Antonella De Matteis, Professor of Biology at the University Federico II of Naples and Group Leader at TIGEM Italy, and Leopoldo Staiano, Head of Research Management and Innovation, screened over 1,300 compounds and using both cell and animal models confirmed that Piclidenoson could restore critical renal functions. Can-Fite Bio Pharma Ltd Israel and Fondazione Telethon Italy are collaborating on the clinical development of Piclidenoson and in 2025 are starting pilot clinical trials at the Bambino Gesù hospital in Rome Italy, led by Dr. Franchesca Emma.

Rapamycin: Prof Claudio Aguilar Purdue University lab screened over 40,000 compounds and identified a couple of FDA approved drugs that could be used in combination (rapamycin and statins), which induce lab-grown Lowe patient cells to start to behave as normal cells. Rapamycin is an immunosuppressant normally prescribed for organ transplants.

The Purdue group has also identified further FDA approved drugs currently used to treat common conditions with the potential to reactivate a specific class of genetic variants that cause Lowe syndrome mutations.

While this strategy may only work for specific patients, it shows the potential for a practical therapy for Lowe Syndrome and paves the way for further research into treatments for other groups of genetic variants.

Drugs can also treat the Brain

In 2024 Research led by Prof Padinjat Raghu at the NCBS India, has shown that drugs that are PIP2 inhibitors may also treat the brain-related symptoms. Please note: UK Lowe patients are recommended to complete the 2024 BEOND survey on behaviour.

Gene Therapy research by the Cure Lowe foundation Denmark EU.

20 years ago, Great Ormond St Hospital UK pioneered the development of stem cell gene therapy, paving the way for research, clinical trials and gene therapy available from the NHS for rare diseases with a genetic cause, and has successfully treated patients.  It is not available for Lowe. 

The Cure Lowe Foundation was founded in 2024 in Denmark by parents Sebastian Honoré and Cecilie Bech Hammer who have a son with Lowe and have decided to dedicate their lives and careers to cure Lowe Syndrome. Sebastian recently presented to the EU on research into rare diseases and lowe syndrome.      

Cure Lowe is developing a gene therapy approach specifically targeting the proximal tubule cells affected in Lowe Syndrome, in collaboration with a biotech company. The foundation has a global team of advisors, patient advocates and scientists (including Stanford USA, Bayer & TIGEM Italy).

Lowe Patient Registry and Database – Citizen Health

To further potential treatments and know what may be applicable to any individual requires a database of all patients worldwide with their DNA mutation. We recommended that all Lowe patients register with the Coordination of Rare Diseases at Sanford (CoRDS) and Citizen Health.

The LSA USA has partnered with Citizen Health that is complimentary to CoRDS, to get all genetic data into one comprehensive database of OCRL mutations for researchers. Lowe Syndrome can be selected, and Languages English and Spanish are supported, more will be added (Mandarin Chinese, French, German, Portuguese, Arabic, Turkish). We recommend families get their DNA mutation letter and upload this and key medical reports. As UK (international) you register with your email or via google, and provide proof of power of attorney and can upload DNA and health records as pdf’s and share a link to the documents (Note I registered my son Oscar and filed DNA, and diagnosis letters).

Concluding Remarks

These are exciting breakthroughs in potential treatments for Lowe Syndrome, and show it is essential to have a database of all Lowe and Dents2 DNA mutations and patent records to find the most effective treatments. 

Please note this is my summary of the potentially therapies intended for families and discussions of next steps and potential clinical trials. Neither myself or the Lowe Syndrome Trust claim any accuracy and cannot be held responsible for any misinformation. We welcome any professional comment and corrections.

Andrew Thomas
CEO Lowe Syndrome Trust

Information

Potential Drug Therapies for Lowe Syndrome

We now have 3 potential FDA approved drug therapies, and a pilot clinical trial project proposal being initiated under ERKNet, the European Reference Network for Rare Kidney Diseases.

As part of the Lowe Family outreach initiative, to prepare for potential clinical trials, the charity is encouraging and assisting families to collect medical records especially the DNA mutation and register with the Sanford Coords database, and will be asking families if they would consider participating in pilot clinical trials.

The charity will also be coordinating with other stakeholders including the Gurdon Institute Cambridge University, Telethon Institute of Genetics and Medicine (TIGEM) and lowe family organisations including the Lowe Syndrome Association (LSA), and the Association of Italian Lowe Syndrome families (Aislo).

A summary for each of the 3 therapies is as follows. This includes a short description and references, and I have shown an indicative cost for the original FDA approved purpose – although this may not represent the costs for Lowe. Information is yet to be available on things like the patients optimum age, or estimate the doses and how the drug may be administered for Lowe Syndrome.

1. Alpelisib (Piqray) – Gurdon Institute Cambridge University UK, University of Zurich, Switzerland and Bambino Gesu Hospital, Italy.

2. Piclidenoson. – Canfite and TIGEM Italy

  • Summary: Can-Fite BioPharma Ltd. (NYSE American: CANF) plans to develop Piclidenoson, originally developed to treat Psoriasis and to research autoimmune inflammatory diseases and COVID-19, for the treatment of Lowe Syndrome based on research by Dr. Antonella De Matteis, University of Naples Federico II, and Program Coordinator of the Cell Biology and Disease Mechanisms at The Telethon Institute of Genetics and Medicine (TIGEM) in Italy. “Piclidenoson is the only compound we have found to date that has shown to be effective in pre-clinical studies. Importantly, we observed that Piclidenoson treatment in mouse models of Lowe syndrome leads to a significant decrease of the urinary loss of proteins in diseased animals,” De Matteis said. “We chose to investigate Piclidenoson based on the availability of extensive scientific data showing its excellent safety, coupled with efficacy in this disease which involves renal, cerebral, and ocular manifestations”.
  • Ordering and Cost (only available today for Research use?): 100 mg, USD $990 https://www.medchemexpress.com/IB-MECA.html
  • Press Release: https://www.tigem.it/newsroom/news-events/new-collaboration-for-telethon-and-canfite-thanks-to-dematteis-work
  • Research Papers: TBC

3. Rapamycin (& statin Rosuvastatin) Purdue University USA

These are exciting breakthroughs in potential therapy for Lowe Syndrome and this is my attempt as a layman’s summary of the potentially available drug therapies, for stakeholders and families for general knowledge and a discussion of potential clinical trials. Neither and myself or the Lowe Syndrome Trust claim any accuracy and cannot be held responsible for any misinformation. We welcome any professional comment and corrections.

Andrew Thomas
CEO Lowe Syndrome Trust