Innovative Therapeutic Approach for Treating Thrombocytopenia Using DNA Damage Repair Inhibitors

Background

Thrombocytopenia is a dangerous condition where the number of platelets in the blood is too low (less than 150 billion per liter), increasing the risk of serious bleeding. This condition may arise in certain immune disorders after chemotherapy, surgery, bone marrow failure (aplastic anemia), HIV infection, and complications during pregnancy and childbirth. Patients currently may be treated with steroids to slow platelet destruction or with platelet transfusions in severe cases. Patients who don’t respond to steroids are treated with medicines called thrombopoietin (TPO) or TPO mimetics. These drugs help increase platelet counts but take several days to work—about 5 days to start and up to 12 days to reach full effect. They can also cause serious side effects like blood clots, damage to the bone marrow, and liver problems. In some patients with abnormal bone marrow cells, these drugs may even lead to leukemia. Additionally, TPO drugs are very expensive, require careful dosing, and often need to be taken for life––either by weekly injections or oral pills with strict diet rules. Because of these challenges, there is a strong need for new and better treatments for thrombocytopenia.

Technology Overview

Boston Children’s Hospital researchers have found a new way to treat low platelet counts (thrombocytopenia) by using drugs that cause or block the repair of DNA damage. Normally, these drugs are used in cancer treatments to kill cancer cells, but researchers found that when they cause DNA damage in cells that produce platelets (megakaryocutes), they actually help increase platelet production. This potential new treatment option involves giving a patient a low dose of DNA-damaging drugs or drugs that stop DNA repair, such as a group called PARP inhibitors, such as niraparib, olaparib, or rucaparib.  This approach could help patients with thrombocytopenia caused by many different conditions, including immune disorders, infections like HIV or dengue fever, blood disease like leukemia, or even those undergoing chemotherapy or surgery. It may also be useful for pregnant patients or those taking certain medications that lower platelet count.

Applications

• Treatment of thrombocytopenia in patients with immune-related conditions.
• Managing thrombocytopenia caused by chemotherapy or surgery
• Addressing platelet deficiency in infections such as HIV, dengue fever, and more
• Treatment for pregnant patients with low platelet counts
• Helping patients on medications known to lower platelet levels
• Use in blood disorders like leukemia and aplastic anemia

Advantages

• Faster increase in platelet counts compared to existing therapies
• Potentially fewer and less severe side effects than current treatments
• Use of low doses may reduce toxicity and risks
• Could be more cost-effective than lifelong TPO therapy
• Oral or injection options available with fewer dietary restrictions
• Broad applicability across many causes of thrombocytopenia