Exosomes are nonviral fragments of cells that can be used for the delivery of genes. Dr. Zempleni has developed targeted milk exosomes and will apply that approach to deliver a critical gene from the PWS region, Magel2, to a mouse model of PWS.
Dr. Theresa Strong, Director of Research Programs, shares details on this project in this short video clip.
BIG PICTURE
This team of researchers has developed a technology, referred to as “Designer” Milk Exosomes (MEs), that enables clinicians to treat PWS. The idea is to load MEs with therapeutic compounds that restore the expression of genes that are deficient in PWS patients to normal levels. Designer MEs are delivered to patients by minimally invasive nasal spray.
SCIENTIFIC ADVANCE
MEs are tiny natural nanoparticles. Both Designer MEs and natural milk exosomes have properties that make them ideal for delivering therapeutic cargo to diseased tissues: (1) The use of MEs is safe for patients; (2) MEs may be delivered by minimally invasive nasal spray or orally; (3) Protocols are available for loading MEs with therapeutic compounds to the brain in PWS patients; (4) MEs are mobile and travel from the site of administration (e.g., nose after nasal spray) to the target site (e.g., hypothalamus in PWS patients); (5) MEs protect therapeutic compounds against degradation during their journey from the administration site to the hypothalamus; and (6) MEs can be produced economically at scale.
The implementation of natural MEs, like any other nanoparticle, in patient care has been decelerated by the following limitations: (1) Immune cells rapidly eliminate nanoparticles; thereby, decreasing the efficiency of treatment. (2) Nanoparticles do not accumulate exclusively in diseased issues, but also deliver their cargo to healthy tissues, which may cause side effects; and (3) Nanoparticles and their therapeutic cargo are rapidly degraded in a particular cell compartment (“lysosomes”) after uptake by target cells, leading to low efficiency of treatment
Designer MEs overcome these limitations and constitute a breakthrough in nanomedicine. For example, the elimination of Designer MEs by immune cells was 12-fold slower than natural milk exosomes, which could lead to increased efficiency of treatment. In ongoing studies, Designer MEs restored the expression of a gene that is deficient in another rare disease to normal levels in the brain.
IMPORTANCE
Designer MEs will enable clinicians to deliver therapeutic cargo to target sites in PWS patients with heretofore unknown specificity and efficiency.
PROJECT AIMS
This project has the goal to develop a treatment for patients with PWS. The researchers will achieve this goal through achieving two aims in wild-type mice and a mouse model of PWS. Aim 1: Optimize Designer MEs to achieve maximal efficiency when treating PWS patients in the future accumulation of Designer MEs in the hypothalamus in wild-type mice. Aim 2: Use a mouse model of PWS to determine if symptoms of PWS can be prevented by treatment with Designer MEs in a proof-of-concept study in a mouse model of PWS.