Compositions and methods for increasing proliferation of adult salivary stem cells
The present disclosure provides methods of increasing proliferation of adult salivary stem cells. The methods include contacting adult salivary stem cells in vivo, in vitro, or ex vivo with an aldehyde dehydrogenase (ALDH) agonist. Increasing proliferation of adult salivary stem cells can be carried out to provide for an increase in the number of adult salivary stem cells in an individual undergoing radiotherapy for head and neck cancer.
1. A method of increasing proliferation of adult salivary stem cells in an individual having a head and neck cancer and suffering from, or being at risk of suffering from, radiotherapy-related xerostomia, the method comprising:
selectively increasing an enzymatic activity of ALDH-3 in adult salivary stem cells in vivo, by administering a therapeutically effective amount of a selective ALDH-3 agonist continuously from 1 week preceding radiation treatment and at least 3 weeks after radiation treatment, wherein said method increases the number of adult salivary stem cells in the individual having the head and neck cancer and suffering from, or being at risk of suffering from, radiotherapy-related xerostomia by at least 25%, and the ALDH3 agonist is a compound having a structure:
or a pharmaceutically acceptable salt thereof.
2. A method of treating an individual having a head and neck cancer and suffering from, or being at risk of suffering from, radiotherapy-related xerostomia, the method comprising:
a) continuous administration of a therapeutically effective amount of Alda-89 up to 1 week before subjecting the individual to radiation therapy;
b) subjecting the individual to radiation therapy; and
c) selectively increasing an enzymatic activity of ALDH-3 in adult salivary stem cells in the individual by continuous administration of a therapeutically effective amount of Alda-89 at least three weeks after radiation therapy, wherein said method increases the number of functioning saliva-producing cells in the individual.
3. The method of claim 2 , wherein the administering comprises orally administering, intravenously administering, locally injecting, or topically applying the Alda-89 to the individual.
4. The method of claim 2 , Alda-89 is formulated in a pharmaceutical composition comprising the ALDH-3 agonist and a pharmaceutically acceptable excipient.
5. The method of claim 2 , wherein the Alda-89 is administered via an osmotic pump.
6. The method of claim 2 , wherein the Alda-89 is administered in an amount of from 25 mg/kg/d to 50 mg/kg/d for the duration of treatment.
7. The method of claim 2 , wherein the Alda-89 is administered in an amount of from 50 mg/kg/d to 100 mg/kg/d for the duration of treatment.
8. The method of claim 7 , wherein the Alda-89 is administered for a duration of from one month to 3 months.