Multiple sclerosis
Multiple Sclerosis (MS) is a severely debilitating autoimmune disease caused by the degeneration and disruption of the myelin sheaths that surround axons of the brain and spinal cord. Myelin loss is associated to neural inflammation, axonal loss and formation of scar tissue in the white matter, leading to a wide spectrum of neurological symptoms, including fatigue, spasticity, functional loss, and pain.
It has been estimated that about 2.5 million of people are living with MS worldwide, with an estimated 10’000 new cases diagnosed in the US every year. In the majority of cases, the diagnosis occurs between 20 and 50 years of age. The most common symptoms include fatigue, visual disturbances, altered sensation and difficulties with mobility.
Treatments for MS mainly target the management of symptoms and attempt to interrupt the damage to myelin sheets. These treatments mostly consist of anti-inflammatory or immuno-modulatory drugs that, given the chronic nature of the disease, expose the patient to serious side effects, with significant impact on their quality of life.
Clinical patterns of appearance and progression of symptoms significantly vary in MS: the most common form of MS is the relapsing-remitting form (RRMS), characterized by episodes of acute worsening of neurologic deficits, including new symptoms and/or the worsening of pre-existing symptoms, followed by periods of total or partial recovery (remissions).
Infusion of autologous hematopoietic stem cells where the expression of PD-L1 is restored could abort the autoimmune mechanism at the basis of myelin disruption providing a curative treatment to MS patients.
Cancer
Cancer is a multi-factorial disease caused by a series of genetic alterations and immune-escape mechanisms resulting in a non-regulated cell growth and proliferation. Tumors have developed multiple immunosuppressive mechanisms to turn down the innate and the effector arms of the immune system, thus compromising most of the immunotherapeutic strategies that have been proposed during the last decade. Programmed cell death-1 (PD-1) plays a major role in tumor immune escape, and the PD-1/PD-L1 interaction enables the tumor to escape the immune response. Targeted modulation of PD-L1 expression might restore an effective immune surveillance of tumors by re-establishing the function of exhausted tumor-specific CD8+ T cells.