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Review
. 2022 Dec 6;12(12):2015.
doi: 10.3390/jpm12122015.

Future Newborns with Opioid-Induced Neonatal Abstinence Syndrome (NAS) Could Be Assessed with the Genetic Addiction Risk Severity (GARS) Test and Potentially Treated Using Precision Amino-Acid Enkephalinase Inhibition Therapy (KB220) as a Frontline Modality Instead of Potent Opioids

Mauro Ceccanti  1 , Kenneth Blum  2   3   4   5   6   7   8   9   10 , Abdalla Bowirrat  10 , Catherine A Dennen  11 , Eric R Braverman  2 , David Baron  3 , Thomas Mclaughlin  7 , John Giordano  2   12 , Ashim Gupta  13 , Bernard W Downs  2 , Debasis Bagchi  2   14 , Debmalya Barh  8   15 , Igor Elman  16 , Panayotis K Thanos  17 , Rajendra D Badgaiyan  18 , Drew Edwards  19 , Mark S Gold  20
Affiliations
Review

Future Newborns with Opioid-Induced Neonatal Abstinence Syndrome (NAS) Could Be Assessed with the Genetic Addiction Risk Severity (GARS) Test and Potentially Treated Using Precision Amino-Acid Enkephalinase Inhibition Therapy (KB220) as a Frontline Modality Instead of Potent Opioids

Mauro Ceccanti et al. J Pers Med. .

Abstract

In this nonsystematic review and opinion, including articles primarily selected from PubMed, we examine the pharmacological and nonpharmacological treatments of neonatal abstinence syndrome (NAS) in order to craft a reasonable opinion to help forge a paradigm shift in the treatment and prevention of primarily opioid-induced NAS. Newborns of individuals who use illicit and licit substances during pregnancy are at risk for withdrawal, also known as NAS. In the US, the reported prevalence of NAS has increased from 4.0 per 1000 hospital births in 2010 to 7.3 per 1000 hospital births in 2017, which is an 82% increase. The management of NAS is varied and involves a combination of nonpharmacologic and pharmacologic therapy. The preferred first-line pharmacological treatment for NAS is opioid therapy, specifically morphine, and the goal is the short-term improvement in NAS symptomatology. Nonpharmacological therapies are individualized and typically focus on general care measures, the newborn-parent/caregiver relationship, the environment, and feeding. When used appropriately, nonpharmacologic therapies can help newborns with NAS avoid or reduce the amount of pharmacologic therapy required and the length of hospitalization. In addition, genetic polymorphisms of the catechol-o-methyltransferase (COMT) and mu-opioid receptor (OPRM1) genes appear to affect the length of stay and the need for pharmacotherapy in newborns with prenatal opioid exposure. Therefore, based on this extensive literature and additional research, this team of coauthors suggests that, in the future, in addition to the current nonpharmacological therapies, patients with opioid-induced NAS should undergo genetic assessment (i.e., the genetic addiction risk severity (GARS) test), which can subsequently be used to guide DNA-directed precision amino-acid enkephalinase inhibition (KB220) therapy as a frontline modality instead of potent opioids.

Keywords: dopamine homeostasis; genetic addiction risk severity (GARS); hypodopaminergia; neonatal abstinence syndrome (NAS); opioids and alcohol common mechanism; reward deficiency syndrome (RDS).

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Conflict of interest statement

K.B. is the inventor of GARS and the KB220 variants and is credited with domestic, foreign-issued, and pending patents. K.B. has entered into an exclusive licensing agreement with Ivitalize, Inc. The other authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Behavioral models are used to classify the phenotypes of substance use disorder (SUD). (Top) The behavioral criteria of SUDs (circled letters) can be sorted into three main categories: impaired control of substance use (Group I), impaired social behavior (Group II), and risky substance use (Group III). (Left) Common rodent experimental models and the SUD criteria that are thought to best approximate them. Note that most models capture multiple SUD features. (Right) Mesostriatal circuits (light purple), including dopamine projections from the ventral tegmental area (VTA) to the nucleus accumbens (NAc), and nigrostriatal circuits (dark purple), including dopamine projections to the dorsomedial (DMS) and dorsolateral striatum (DLS), generally have dissociable roles in different components of major SUD models. The middle panels list the most clearly defined roles for these two systems in each SUD category.
Figure 2
Figure 2
Representative cross-correlation maps show five subjects: placebo-controlled and KB220Z-treated rats. The maps correspond to the resting-state connectivity for the NAc (highlighted in green in the atlas map above the figure; only the left seed is shown). Note the distributed but significant connectivity between various brain regions and the NAc in the placebo subjects. KB220Z increased connectivity, especially between the left and right accumbens, dorsal striatum, and limbic cortical areas, such as the anterior cingulate, prelimbic, and infralimbic regions. Correlation maps for the representative subjects are presented at a threshold of 0.3 ≤ z ≥ 1.2 [135] (with permission).
Figure 3
Figure 3
Schematic of our proposed model to treat and identify genetic antecedents and to provide a way of inducing “dopamine homeostasis.”
Figure 4
Figure 4
Precision addiction management platform [210] (with permission).
Figure 5
Figure 5
This schematic represents the paradigm shift required to circumvent the use of powerful opioids to treat opioid-induced NAS. We propose to couple the GARS test with DNA-directed precision KB220 therapy to detoxify and maintain patients with NAS using a non-opioid nutraceutical neuronutrient alternative.
See this image and copyright information in PMC

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