Photo: PLN Foundation
Technology developed by pioneering small interfering RNA (siRNA) chemists Anastasia Khvorova, PhD, the Remondi Family Chair in Biomedical Research and professor of RNA therapeutics at UMass Chan Medical School, and Hassan Fakih, PhD, a postdoc in her lab, has been licensed from UMass Chan by PLaN Therapeutics, a nonprofit biotechnology company fully owned by the PLN Foundation.
The collaboration aims to further develop an allele-specific siRNA-based therapy for the treatment of PLN-R14del genetic cardiomyopathy. Under the agreement, PLaN therapeutics will retain exclusive rights to the product.
“We’re excited to be partnering with PLaN Therapeutics to develop a potential siRNA therapeutic for PLN-R14del cardiomyopathy,” said Dr. Fakih. “PlaN’s expertise in PLN-R14del cardiomyopathy is instrumental to translating this science from the bench to the clinic where it will benefit patients and their families.”
“This collaboration represents a critical step in translating decades of groundbreaking scientific research into a potential therapy for patients living with PLN-R14del cardiomyopathy,” said Pavlina Konstantinova, PhD, CEO of PLaN Therapeutics. “It provides hope to patients and families who currently have very few options.”
PLN-R14del cardiomyopathy is caused by a dominantly inherited mutation in the phospholamban (PLN) gene, which leads to progressive heart failure and life-threatening arrhythmia. Currently, the disease is treated with general heart failure medication, but this has no effect on the disease’s progression. Development of symptoms always results in end-stage heart failure for which the only treatment is heart transplant.
siRNAs are short, double-stranded RNA molecules (around 20-25 base pairs) that can silence specific genes by targeting complementary messenger RNA (mRNA) for degradation after transcription, thereby preventing translation. Given the ability to knock down, in essence, any gene of interest, siRNAs have generated a great deal of interest in translational biomedical research. However, delivery of siRNA to target tissues, such as the heart, has been challenging because of potential off-target side effects and a lack of chemical durability that limits efficiency and effectiveness.
Under the collaboration agreement, PLaN Therapeutics will work closely with Dr. Khvorova and Fakih to develop clinically validated chemical modifications of an allele-specific siRNA molecule that selectively silences the mutated PLN gene without interfering with the expression of the healthy allele.
By modifying specific chemical groups, the researchers aim to improve key therapeutic properties, such as durability, distribution and target engagement. Researchers will focus on identifying, optimizing and further developing the most effective allele-specific siRNA molecule for addressing the PLN-R14del mutation. This approach is intended to support a subcutaneous dosing regimen of approximately once every two to three months, offering a potentially patient-friendly treatment profile.
“With our technology, we can make the siRNA oligonucleotide in a form that can reach the heart,” said Khvorova. “This work is a big step towards solving the delivery problem for siRNAs in the heart and one step closer to a clinical treatment for PLN-R14del cardiomyopathy.”
PLaN Therapeutics is a nonprofit biotechnology company dedicated to developing disease-modifying therapies for PLN-R14del cardiomyopathy. Originating from the PLN Foundation, the company focuses on translating cutting-edge science into treatments that address the root cause of this inherited heart disease. PLaN Therapeutics is committed to bringing this therapy to PLN-R14del patients at a fair price.
