Aclarubicin for the Treatment of Retinal Vasculopathy With Cerebral Leukodystrophy
Status:
Completed
Trial end date:
2020-07-23
Target enrollment:
Participant gender:
Summary
The goal of the investigator is to utilize Aclarubicin to treat patients with Retinal
Vasculopathy with Cerebral Leukodystrophy (RVCL), a rare and devastating genetic disease with
no available specific treatment. RVCL results from a mutation in the tail end of the TREX1
(Three Prime Repair Exonuclease 1) gene, a major deoxyribonucleic acid (DNA) repair enzyme.
The RVCL-specific mutations cause expression of a truncated and mislocalized protein. RVCL is
an inherited disorder whose symptoms begin at middle age and initially predominantly affects
the eye and brain. Because it is an 'autosomal dominant' disease, it strikes both males and
females equally. A person with RVCL has a 50-50 chance of transmitting the gene to each
child.
The investigator's published studies demonstrated in a mouse model for RVCL and in vitro
studies with patients' cells that defects were corrected by use of Aclarubicin, an
anthracycline antibiotic often used to treat cancer. Thus, there is a strong rationale for
conducting a clinical trial of aclarubicin in patients with RVCL.
The dosage to be initially administered to RVCL patients initially will be < 10% of that
typically used in cancer therapeutics and will be given monthly on four consecutive days for
six months. Patients will undergo assessments every six months to determine disease response.
Patients that do not have clear objective response may be dose escalated by 1 dose level with
permission of the principal investigator permitting the patient has not previously
experienced any toxicities requiring dose modifications. We will evaluate the safety and
clinical efficacy of Aclarubicin for the treatment of RVCL and evaluate its effects on
cellular function. This work will generate the first clinical research data on the
investigational product's utility in treating RVCL.
Patients are followed for at least 2 years upon completion of Aclarubicin administration
completion. We are not longer administering the drug, but are in the post-drug follow up arm
of the study.